Myriad Genetics, Inc., the owner of the patents, brought the case to Federal Court of Appeals, which overturned the lower court’s decision on July 29 in a 2-1 ruling that has, at least for the time being, reaffirmed the patentability of human genes. Notably, the Obama Administrations Justice Department broke with the Patent and Trademark Office, a co-defendant in the case, in filing an amicus brief in support of the plaintiffs claim that the genes should not be patentable.

The Appeals Court also upheld Myriad’s patents on procedures for therapeutic research on BRCA 1 and 2, but agreed with the lower court that Myriad’s processes for “analyzing” and “comparing” the genes are not patentable. Despite this small concession, it does not seem likely that this will make it easier for scientists who are unaffiliated with Myriad to conduct significant research on BRCA 1 and 2.

“[Myriad’s] short sequence claims [on BRCA 1 and 2] will continue to pose problems,” said Arti Rai, the Elvin R. Latty Professor of Law at Duke Law School and an expert in patent law and innovation policy, in an interview with Science Progress. “I’m not sure that the plaintiffs at the end of the day are in a better position,” she said, noting that they will probably run into many of the same patent infringement issues that they have in the past.

Though the full effects of this ruling on the biotechnology industry and the cancer research community remain to be seen, it is by no means the last word on the issue of gene patents. The plaintiffs, a coalition of doctors, patients, breast cancer researchers, research institutions, and medical associations, are expected to ask for an en banc rehearing—in which all of the justices in the court of appeals would sit for the case, instead of a panel of only three—or appeal the case to the Supreme Court. The Supreme Court can let the appeals court decision stand, or take up the case and issue its own ruling.

Why were genes patentable in the first place?

Patents for biological materials have long been a contentious issue, and decades of Supreme Court cases have interpreted U.S. patent law, which was written over 200 years ago, to fit the complexities of property in modern biotechnology. Currently, the United States Patent and Trademark Office, or USPTO, can issue patents for genes, animals, bacteria, and plants—as long as they are, according to the Patent Act of 1790, “any new and useful process, machine, manufacture, or composition of matter, or any new and useful improvement thereof.”

Patents for biological materials must also fit the “product of nature doctrine,” a standard that excludes entities that occur in nature from patent eligibility. The doctrine was first used in ex Parte Latimer (1889) when the U.S. Patent Commissioner rejected a patent application for isolated pine needle fibers. It was further developed in Funk Bros. Seed Company vs. Kalo Inoculant Co. (1948) when the Supreme Court ruled that natural phenomena and processes are “free to all men and reserved exclusively to none,” and rejected a patent application for a novel mixture of bacteria and soil.

Genes, bacteria, and animals seem like they should fall in the “product of nature” category, but later Supreme Court decisions have shown that sufficient modification of a naturally occurring entity can make it enough of a “new manufacture or composition of matter” to be eligible for a patent. In Diamond v. Chakrabarty (1980), the Supreme Court permitted a patent for a genetically engineered bacterium. In 1984, the USPTO granted a patent to the creators of the “oncomouse,” a mouse that was engineered to express cancer genes in every cell in its body.

Thanks to the precedents set by these and other cases, the USPTO has issued over 40,000 gene patents to date. Myriad Genetics justified their own gene patents via the argument that isolated forms of BRCA 1 and 2 do not occur in nature, and that such isolation results in the formation of different chemical bond structures within the molecules.

In 2010, the New York district court invalidated the BRCA 1 and 2 patents on the basis that the genes, even when isolated, have not acquired any changes to the fundamental nature of its DNA sequence or the genetic information they contain. The majority opinions of the recent federal appeals court ruling, on the contrary, agreed with Myriad Genetics’ original justification for the patent. They also noted that isolated BRCA 1 and 2 can be modified in the lab to form cDNAs, which can then be used to develop genetic probes and markers—a process for which BRCA 1 and 2 are only useful if they are isolated. The dissenting opinion by Justice William Bryson, however, held that the BRCA 1 and 2 genes on their own should not be patentable because Myriad did not discover the genes or use any novel techniques to isolate them. However, he held that the cDNAs, since they are modified by researchers, are patentable.

Gene patents and scientific progress

While the technicalities of what constitutes a “product of nature” or a “manufacture” seem to spark disagreement in the case of isolated genes, the stakes are high for a decision on gene patentability.  According to the U.S. Constitution, patents are supposed to “promote the Progress of Science and useful Arts” by giving inventors the exclusive right to exploit their inventions for a limited period of time.

This is true much of the time, as patents encourage innovation and scientific progress by ensuring that inventors can reap the benefits of their work. Plus, a ruling that would invalidate all existing gene patents could potentially have far-reaching negative effects on patent holders and the biotechnology industry in general.

But the plaintiffs in the Myriad case disagree, and argue that gene patents significantly impede, rather than promote, scientific progress. Researchers from Oncormed and the University of Pennsylvania Genetic Diagnostic Laboratory, or GDL, who are plaintiffs in the case, were already conducting research on and offering their own diagnostic genetic testing services for BRCA 1 and 2 when Myriad acquired its patents on the genes and associated research and testing processes. However, these researchers were forced to stop conducting diagnostic testing and therapeutic research in the late 1990s after Myriad sent them cease and desist orders for patent infringement.

Myriad’s vigorous enforcement of their BRCA patents has rendered them the sole provider of genetic testing for BRCA 1 and 2 in the United States. As a result, women who wish to learn of their genetic risk for breast and ovarian cancer cannot turn to other diagnostics providers for confirmatory tests. Nor can patients seek cheaper alternatives to Myriad’s services, whose BRCA tests cost between $250 and $4,000.

In addition to limiting the competition among diagnostic test providers, Myriad’s monopoly on BRCA also allows them to control the progress of BRCA research. Other scientists cannot research potential improvements for BRCA therapeutics or expand scientific understanding of high-risk BRCA gene mutations without infringing Myriad’s patents.

An issue of authority

The federal appeals court opinions acknowledge the question of whether gene patents promote or impede scientific progress, but instead of answering it outright, they defer it to Congress and do not deal with the case beyond the scope of patent law. “If the law is to be changed, and DNA inventions excluded from the broad scope of [patent law] contrary to the settled expectation of the inventing community, the decision must come not from the courts, but from Congress,” wrote Judge Lourie in the court opinion.

While Congress might be in a better position than the judicial system to consider social, economic, and scientific implications of gene patents, they have never been particularly successful in passing legislation concerning patentable subject matter. “These are policy issues to be decided by Congress, but the fact is that Congress is unlikely to act in this area,” said Rai.

If Congress doesn’t speak out on the issue, the Supreme Court has the authority to make its own decision on the patentability of genes. “For better or for worse,” said Rai, “a court decision in this area may end up being the final word.”

As such, the federal appeals court ruling is just another step in what has been, and what will continue to be, a long process of sorting out property in the genome. The final outcome for the genetic research community and gene patent holders remains to be seen.

Michelle Spektor recently completed her internship at Science Progress and will complete her bachelor’s degree at Cornell University this year.

Historically, neuroscientists have had a range of tools to manipulate and observe neural circuits in the brain. These techniques, however, have often lacked the ability to isolate the contribution of specific neurons or types of neurons to the overall network. With optogenetics, researchers can now discretely control neuronal activity by using pulses of light to activate or inactivate specific populations of neurons. These tools are giving neuroscientists the potential to unlock many of the remaining mysteries of how individual groups of cells in the brain control perception and behavior.

The term optogenetics was first coined by one of its pioneers, Karl Deisseroth at Stanford. The technique, which recently won the 2010 Nature Methods method of the year award, makes use of a group of ion channels and other proteins discovered in bacteria and algae called “opsins.” These proteins are light sensitive and can therefore be activated by pulses of light of an appropriate wavelength. Depending on the opsin expressed, this will either excite or inhibit the neurons. The expression of opsins in mammalian neurons is achieved by inserting the encoding DNA into the target cells, which then produce the opsin proteins. The process of DNA addition is called transfection, and is typically accomplished by using a specially selected virus as a carrier to deliver the new DNA. Variants in the viral delivery and DNA coding sequence allow for specific subtypes of neurons to be targeted. Once opsins are expressed in the neurons, the firing rate can then be controlled in vivo by light from an implanted fiber-optic cable or through a small window in the skull.

This technique gives researchers enormous flexibility and control of the behavior of specific cell types in a given brain region. Spatial resolution comes from the location of the injection and the neural cell-type specificity of the viral vector. Temporal control is produced by the frequency of the delivered light pulses, which via the opsins drives the cells to fire at the same frequency as the pulses of light, or alternatively prevents them from firing at specific times.

For example, a group of neurons in a specific area of the brain could be transfected with an opsin that excites the cells, and then is activated at various frequencies to see how this changes the animal’s perception of a stimulus directed to this area of the brain. It can also be used to completely silence a set of neurons during specific behavioral tasks in order to determine the effect of those neurons on that behavior. With this level of precise control, many systems neuroscience questions that had imprecise answers previously can now be addressed by observing awake, behaving animals.

Some of the recent articles published using this technique have demonstrated new insights into previously vexing problems in neuroscience. For example, there has been a tremendous amount of debate about the mechanism of deep brain stimulation, or DBS, utilized to treat movement disorders resulting from Parkinson’s disease.

This treatment uses electrical stimulation targeted to a region of the brain involved in motor output and control, and its mechanism of action is not well understood. It has previously been difficult to assess whether this intervention affects the neurons nearby the electrode directly, the inputs to those neurons, or the targets of the output from these neurons in this circuit.

Researchers utilized a mouse model of Parkinson’s disease and optogenetics to dissect the circuits of the brain involved in the response to electrical stimulation of the targeted area. Their results suggest that rather than leading to a simple excitation or inhibition of the neurons in the targeted area, DBS is activating connections arising from another area, and that this activation is necessary for the effectiveness of the treatment.

Another recent article demonstrated the importance of a single type of neuron to cocaine addiction in mice, suggesting a target for future clinical interventions. Because this particular type of neuron represents only 1 percent of the cells in the investigated area (the Nucleus accumbens), they have been difficult to study up until now, and their function has been the subject of much debate in scientific literature. The precise genetic targeting of the opsins allowed for just this population of neurons to be manipulated during the experiment.

The implications of this new technology for the field of systems neuroscience are profound. Its potential is being realized as the technique is implemented more broadly and more difficult circuits and systems are teased apart. A better understanding of the circuits underlying psychiatric and neurological disorders will hopefully also lead to improved clinical treatments.

One question for the future is whether or not these new techniques may be directly used to treat some human disorders as well. For example, a future version of DBS might be coupled with optogenetics to provide more specific targeting of cells in the basal ganglia, directly affecting the firing patterns of the cells responsible for disrupted movement in Parkinson’s disease. In addition, research efforts in the past year have successfully demonstrated the feasibility of utilizing optogenetics in nonhuman primates. Use of this technology in humans, however, would combine the ethical dilemmas of gene therapy with those of brain-machine interfaces such as DBS. While the road to safe and efficacious use of this technology for treatment in humans is uncertain, it is already providing great benefits to scientists in understanding circuits and their complex regulation in the brain.

As Congress turns back this week to the continuing resolution to fund the government through the end of fiscal year 2011, it is important that we keep in mind the essential role of federal funding in facilitating scientific advances like optogenetics. The original project in Dr. Deisseroth’s laboratory, the first attempt to integrate the microbial opsins into mammalian cells, was funded by a grant awarded by the National Institutes of Mental Health and National Institutes of Health, as are many of the above-mentioned projects that followed. The first scientists describing the light-sensitive proteins in 1971 could not have predicted that their findings would lead to such a profound change in neuroscientific research. These discoveries are one of the best arguments for continuing to fund basic biological research as well as more translational research: We often don’t know where the breakthroughs are going to come from that will be the basis for the next generation of treatments for disease, or that will allow us to better understand the complex systems that make up our daily habits, thoughts, and decisions.

John A. Wolf, Ph.D., is a neuroscientist at the Center for Brain Injury and Repair in the Department of Neurosurgery at the University of Pennsylvania.

Cody hails from a family with a special status in American life:  Her father is two-time Indianapolis-500 winner Al Unser Jr. and her grandfather, Al Unser Sr., is also a repeat winner of the iconic American race, as is her uncle, Bobby Unser. The Unser’s are a veritable racing dynasty, with a total of 9 Indy-500 titles between them. Coming from a family that is considered American royalty by some has certainly helped Cody to tell convey her message. But Cody knows she cannot rely on her family’s notoriety alone.

“As an advocate, I’m trying to understand more about how to use my personal story and bring it together in a more powerful way,” she says. “I don’t want to just use my story, I want to back it with facts and the truth. And what these [embryonic stem cells] are and what the science is.”

With the help of the First Step Foundation, which she runs with the help of her family, Cody travels the country to raise awareness for spinal injuries, paralysis, and research funding for potentially life-changing therapies such as embryonic stem cells that could one day allow her to regain the use of her legs. She was even asked to testify before the Senate Appropriations Committee in September (you can watch the video here). Last Friday, Science Progress’s Jonathan Moreno had a chance to catch up with Cody to talk to her about biopolitics, her future, and educating congress and the public about the importance of science and technology in medicine and society.

“People who walk don’t necessarily think of their shoes as technology as much as I do my wheelchair. There’s a difference there that is interesting,” says Cody. “I rely on [technology] just to get around, from point A to point B. So I’ve learned so much about how technology influences science and health… there are two different avenues it seems… to think of the body not only as biology but also as engineering.”

Cody’s life is intrinsically connected to technology. “I think for a lot of people with paralysis or spinal cord injury, rehab and maintaining their body is a daily struggle—our bodies are deteriorating at a faster rate than most people.” Besides her wheelchair she uses a mechanical standing frame to help keep her bones strong, special scuba gear to allow her pursue her passion of diving, and special electrodes which stimulate her nervous system, allowing her to help maintain leg muscle by peddling on a special bike. From everyday use of technology that young people in her generation have become accustomed to—like Facebook—to the devices that she relies on to live a normal life and maintain her body, to her activism on behalf of millions whose futures literally depend on the rate of advancement of new technologies, Cody knows that she has a special relationship with science and technology.

“I think science gets at the core of our human vulnerability. Both in a negative and a positive [way]. Science has evolved so fast and it freaks people out because we don’t want to lose what makes us human. Science brings about cures in the medical world, stem cell research one day will be able to treat disease and disability. But I don’t think that we will ever lose what makes us human. Science will never be able to push us back that far.”

Science and health policy have a profound impact on Cody’s life, a fact which she thinks has shaped her decision to pursue a career educating Congress and the public about the importance of science and health policy. As an advocate for paralysis victims, Cody represents a population of as many as 6 million Americans living without the use of some part of their body. Of her testimony before the Senate Appropriations Committee on the promise of human embryonic stem cell research, Cody recalls:

“Basically you are the voice of a population whom science can influence and benefit. I was so humbled to be given the opportunity to speak on behalf of a huge community. I represent the spinal chord injury community, but I don’t know what it’s like to have diabetes, Parkinsons… [other diseases that could be cured by stem cell research]. To try to bring everyone together in the same world [to advocate for human embryonic stem cell research] was really cool. To be able to speak on behalf [of that] was something I’ll never forget.”

Ultimately, Cody is humble about the advantages she has had which enable her to pursue her passion for sound science-based healthcare and research policy, and as an advocate for spinal cord injury victims.

“I didn’t have to fight for my right to work or to enjoy my life like anybody else. To be able to now represent that population and not think about those things and move forward…I think the fight is out there. And the fight is different this time.”

Listening to Cody, it’s clear she’s more than up to the fight.

]]> http://scienceprogress.org/2010/11/interview-with-youth-crusader-for-stem-cell-research/feed/ 0 http://scienceprogress.org/2010/08/thrown-back-to-the-90%e2%80%99s/ http://scienceprogress.org/2010/08/thrown-back-to-the-90%e2%80%99s/#comments Mon, 30 Aug 2010 18:07:11 +0000 Jeanne F. Loring, Ph.D. http://www.scienceprogress.org/?p=6773 In 1998, a handful of laboratories around the world were trying to generate human embryonic stem cells from five-day old embryos that had been discarded by in vitro fertilization clinics. The feat had been accomplished for mouse embryos 17 years earlier, and mouse embryonic stem cells had a tremendous, Nobel Prize-winning impact on basic and translational medical research. Unlike the mouse ES cell research, the human embryonic stem cell efforts were funded exclusively by private funds from companies.  Because of the so called Dickey-Wicker amendment, the National Institutes of Health was prohibited from providing support for the use of human embryos to make these cells.

Scientists are good at overcoming barriers, and the first human embryonic stem cell (or, hESC) lines were made in 1998 in the United States and Australia. Three years later, there were around 20 documented hESC lines in countries around the world, and on August 9, 2001, President George W. Bush decreed that federal funding would be allowed for this small number of existing lines; he recognized that hESCs were key to launching a new era in medicine—regenerative medicine.

Progress since 2001 has been nothing short of astonishing. Research using these 20 hESC lines created a foundation that led to remarkable breakthroughs that are already improving medicine. From this hESC research we learned how to turn skin cells into hESC-like cells, and how we may be able to treat diseases that are currently incurable. Knowledge about hESCs is the basis for all of regenerative medicine, including ideas about how to improve the limited abilities of adult stem cells.

Then, on August 23, 2010, after millions of dollars in NIH investment in hESC research, a pair of disgruntled scientists convinced a U.S. District Court judge to issue a preliminary injunction barring federal funding of work involving hESCs. So, a dozen years after hESC research was launched, and well into the development of therapies using these remarkable cells to improve human health, it is possible that this judgment will send us back right back to the stem cell dark age, 1998.

Why?  It’s about money. These two researchers working on adult stem cells were afraid that if the NIH continued to fund hESC research then it was going to make it harder for them to get money for themselves. This argument is ridiculous to anyone who knows anything about how the NIH works, and we fervently hope that this foolishness is resolved quickly.

But let’s look at the damage that will be done if this injunction holds. The meeting of the International Society for Stem Cell Research, held in San Francisco this June, drew a crowd of more than 3,000 scientists from the United States and many other countries.  The society was formed in 2002 to bring together the ever-growing group of scientists whose work was sparked, directly or indirectly, by Bush’s policy. Among the scientists were the next generation, 20- and 30-somethings, who were going to lead the charge for development of hESC therapies in the future.

What will become of these scientists if the injunction stops their research? The first effect will be that some will almost immediately lose their jobs when their NIH funding is stopped. Many graduate students and postdoctoral researchers are supported by the NIH; those working with hESCs will have to find other jobs. This is terrible for the individuals, but it may be worse for the millions of people who will acquire Type I diabetes, Parkinson’s disease, heart disease, and suffer from strokes in the next 20 years. Without this generation of stem cell scientists, the chances of regenerative therapies for these disorders will be miniscule.

The NIH has invested money, and thousands of scientists have invested years of their lives in order to make hESC-based therapies possible. To stop now will mean that all of those dollars and all of that sacrifice will be wasted. Other countries who continue to fund hESC research will rapidly surpass our nation. China, for example, has invested greatly in hESC research. The end of U.S.-based hESC research will mean that the benefits, both medical and financial, will go elsewhere.

We can’t afford the loss of intellectual power that this injunction will bring. In 2010 it would be a tragedy to set hESC research back to 1998 in the United States while scientists in other countries (and perhaps many now working and living here who will soon alight to Asia) forge ahead.

Jeanne F. Loring is a professor and the director of the Scripps Research Institute Center for Regenerative Medicine in La Jolla, CA.

Lots of folks seem to think we have too much regulation of drugs and devices already—among them Paul Howard at the Manhattan Institute and Scott Gottlieb at the American Enterprise Institute—so much so that it is choking innovation to death. But, if that is so, then why are there so many scandals?

One possible answer is that the companies know they have problems but sit on that knowledge. If that’s sometimes (or oftentimes) the case, then we need a regulatory system that can get around that kind of immoral behavior. We don’t have that system.

What we have is a regulatory system that is too skewed toward looking at the earliest stages of research. Moreover, the way it is designed makes recalls almost inevitable. The diabetes drug Avandia is the latest in a long parade of failures of our current post-clinical trial drug approval process.

Avandia went through the usual approval process with the U.S. Food and Drug Administration. The drug was a blockbuster. But sales began to fall after a 2007 study of people taking the drug suggested that Avandia could cause heart attacks and strokes. I first learned about this while serving on a bioethics advisory board for GlaxoSmithKline, the developer of the drug—a panel that was looking at research ethics issues in poor nations. The panel, on which Science Progress Editor-in-chief Jonathan Moreno also served, came to an abrupt halt.

In response, the FDA put a black-box warning on the drug telling doctors of the heart attack risk. GlaxoSmithKline was not happy. There was a lot of back and forth about the safety of the drug. Over the past few months more evidence become public that shed doubt on Avandia’s safety. Worse, it appears the company withheld data about serious side-effects. The FDA appointed an advisory panel this July to consider these allegations, but the panel itself quickly got caught up in charges of conflict of interest among its members. It is likely that more black-box warnings to doctors will follow, should GlaxoSmithKline choose to keep Avandia on the market.

Avandia is not alone. The drug’s problems in the marketplace follow hard on the heels of Prempro, a hormone replacement therapy made by Wyeth Pharmaceuticals, now part of Pfizer Inc., which became caught up in lawsuits alleging it caused breast cancer. More recently, the FDA released a warning about the Afluria flu vaccine, made by CSL Ltd. of Australia, concerning high fever and seizures. Prior to that was Merck & Co.’s widely publicized recall of Vioxx, which came after problems with Astra Zeneca’s Seroquel, Abbott Laboratory’s Meridia, Pfizer’s Rezulin, C.R. Bard Inc.’s G2 filter, Bayer’s Baycoll, Boston Scientific Inc.’s Express Stent, and on and on.

So is there a real phenomenon here or just more PR associated with recalls? And if there are more recalls going on then what is wrong with the oversight of new drugs and devices?  It is not clear from the literature whether there are more recalls taking place in recent years—there is no real database that would show such a trend. There are certainly more stories about recalls and more people studying the objectivity of the marketplace surveillance being done by pharmaceutical, biotech, and device companies.

No one seems to have reliable numbers on recall trends, yet the Institute of Medicine and other groups still warn that the existing system of drug protections after the FDA approval process is complete does not seem adequate to handle the products that are reaching the market. Fortunately, there is a way to fix the system.

The major problem today is that too many lousy or dangerous drugs and devices get to you without adequate safety review because drug and device regulation is heavily weighted in the United States toward early stages of research. Every drug has to be tried in animals to roughly determine safety. Then drugs are introduced into a small number of humans to further check safety—so-called phase one trials. Then dose and mode of administration are checked for safety, biological activity, and signs of effectiveness—phase two. Only after all this safety testing is a drug or device ready to go to phase three clinical trials. In these studies hundreds or sometimes thousands of subjects are recruited to receive the drug or product for periods of time that range in nearly every case from a few months to a year.  Phase three trials are almost always placebo controlled randomized, blinded studies.

So there is a lot of effort to try and make sure that subjects are not hurt in phase three trials. The deaths of subjects in phase one clinical trials, among them Ellen Roche and Jesse Gelsinger in early stage studies over a decade ago seem to have reinforced regulatory anxiety about the risk of deaths in first in-human studies.

Meanwhile, the weakest link is the fourth and final step in the research process—phase four—in which drugs are to be monitored when out in actual use in the world for adverse events and problems. Drug companies sometimes promise to do these trials to get final product approval but don’t. These studies are heavily weighted to support the funders of these studies, Big Pharma, which results in much more rosy reporting then studies done by independent groups.

Reporting of problems in phase four is left to doctors and patients who rarely do so.  And there is no systematic tracking of a subpopulation taking new drugs or other medical products to see what is going on with real patients in real world conditions. Deaths have to mount rapidly and obviously to get regulatory or physician attention before phase four studies are ever seriously undertaken.

But a lack of independent, well designed phase four trials is not the only problem.  Approving drugs based on current standards for phase three testing has its own built-in limits. Testing drugs and devices in randomized, blinded, placebo control trials is great, but it means that approval is given on the basis of highly controlled studies on highly selective populations—often subjects who are not that old, not that sick and are highly compliant. That’s not the real world, where patients take lots of drugs, some legal some not, are poorly compliant, have multiple diseases, and can be very old or very young.

So what looks safe in a phase two or phase three study can prove lethal when given to real people in uncontrolled, unsupervised environments. What’s more, phase three studies are also relatively short. What looks safe after three months exposure or six may not be after three or six years.

The seemingly endless parade of horrors of FDA approved drugs gone bad merits a reexamination of a regulatory system that is not keeping us safe.  The issue is not too much bureaucracy and too much red tape, but a strategy of safety that puts the emphasis in the wrong place—early not late—and then uses techniques that by themselves cannot ensure safety for real people in the long run.

Update August 17 2010: CNN Money reported that the number of drug recalls in the U.S. surged to 1,742 in 2009, up 309 percent from the 2008 level. Recalls so far in 2010 are also on pace greatly exceed previous levels. However, not all of these recent recalls were due to the drugs themselves being unsafe—some were due to problems with the manufacturing process of generic, over-the-counter drugs.

Arthur Caplan, PhD, is the Director of the Center for Bioethics and the Sidney D Caplan Professor of Bioethics at the University of Pennsylvania

Last week the Food and Drug Administration gave its first approval for a clinical trial of an embryonic stem cell treatment. Embryonic stem cells are special because they can grow, or differentiate, into any kind of human tissue. Many believe they hold great promise for treating a wide range of diseases and disorders, from Alzheimer’s to cancer to spinal cord injuries to blindness.

The FDA had put the application from biopharmaceuticals company Geron Corp, which produced the cells, on clinical hold after some mice given the treatment developed tiny spinal cysts. But another animal study found no cysts. The testing will involve patients with recent spinal cord injuries, who will receive infusions of embryonic stem cells that have been differentiated into cells that can produce myelin, the coating that conducts electrical impulses in the spine.

There is no expectation that this cell treatment would magically regenerate spinal cords, though much could be learned from a greater understanding of how new cells integrate into damaged tissue. Rather, the goal is to facilitate some improved potential for movement along with strenuous physical rehabilitation. It is thought that recently injured patients might be more susceptible to improvement.

The company is reported to have spent $150 million to get the trial approved.

The stem cells developed by the company are derived from an embryo that was left over following fertility treatment. It had to be donated with full informed consent by the couple. Geron was able to proceed with the lab work to develop the treatment in spite of the Bush administration policy that severely limited federally funded embryonic stem cell research.  Several years ago the company produced dramatic footage of injured rats that had been treated with the cells and were able to regain movement.

The greatest concern that experts have about the trial is that potent cells injected into the spine might develop into tumors called teratomas. This worry explains the FDA’s cautious approach.  Although there are nonembryonic stem cell treatments for spinal cord injury that have been tried, they have been criticized for inadequate safety data from animals and unclear explanations of surgical procedures. By contrast, owing to the potential harm, novelty, and public controversy, the Geron trial is surely among the most intensively reviewed proposed clinical trials in history.

All this does not guarantee success, of course, nor does it guarantee that no harms will result.  This is biology in the real world, not a computer simulation. But it does establish a reasonable regulatory pathway for human embryonic stem cell treatments for serious diseases that currently have only very inadequate therapies, a milestone that would have been all but political science fiction just a few years ago.

Meanwhile, thanks to the Obama administration’s responsible stem cell policies, dozens of new embryonic stem cell lines are being approved for federally funded research under grants from the National Institutes of Health. This should lead to more academic centers engaging in targeted research with these and other stem cells sources.

While the FDA’s approval of the Geron trial is just a small incremental step forward for potentially lifesaving research, it represents a significant break from past bickering, and raises the inkling of hope that someday we may wonder what all the shouting was about.

Jonathan D. Moreno, Ph.D., is the David and Lyn Silfen University Professor of Ethics and Professor of Medical Ethics and of the History and Sociology of Science at the University of Pennsylvania, and the Editor-in-Chief of Science Progress.

The promise of the field of synbio as a whole is that scientists will be able to employ this type of genome synthesis to create customized life forms for a wide array of purposes. The peril is exactly the same as the promise.

Rising to this demanding task, committee chair Amy Gutmann, president of the University of Pennsylvania, led a constructive conversation by asking pointed questions and periodically distilling the major points of contention and agreement among the various discussants. Drew Endy of Stanford University, a pioneer of synthetic biology, praised the meeting as the best conversation on synthetic biology that he has ever seen. The reason, he said, was that the most striking development over the course of the two-day conversation was its shift from simply avoiding the risks of synthetic biology to carefully harnessing its benefits in a way that is attuned to broader global challenges.

Jim Thomas of the ETC Group, a Canadian green civil society organization, prompted this major turn in the conversation towards synbio’s global socio-economic implications by emphasizing the economic displacement that takes place when a new technology like synthetic biology enters the global economy. For instance, a synbio technology that allows an industry to grow an organic product in a vat for a lower cost than it could on the land would destroy the livelihood of thousands of farmers the world over. Thomas’s position was distinctly green and scientifically prohibitionist since he advocated a moratorium on the commercial or environmental release of synthetic biology products.

Indeed, upon further questioning by the commission, it seemed as if he were advocating more of a ban than a moratorium since he could not arrive at a concrete “bottom line” for the safety and equity standards that synbio would have to meet for the moratorium to be lifted. He suggested the creation of new “social technologies” for assessing the social and economic impacts of technology and building democratic consensus among global populations. He noted that there is currently no democratic way of allowing the release of synbio technology, to which Dr. Gutmann retorted that there is no democratic way of banning it either.

The dialogue prompted Allen Buchanan of Duke University to provide a more tech-positive counterpoint to Thomas’s claims about the vulnerability of the global environment. Buchanan argued that objections about “playing god,”  “interfering with nature,” or “altering human nature” are often used to smuggle in assumptions about nature being inherently harmonious, stable, or balanced.  He explained that nature is in a constant state of flux and that evolution is an imperfect process that “at most…fleetingly approximates maximal biological fitness.”

Assumptions about nature being benign or harmonious automatically stack the deck against any biotechnologies. Since risk can never be completely eliminated, Buchanan encouraged the commission to educate the public about risk management, its costs, and the importance of institutional designs that create the incentives for accurate risk management. And he did agree with Jim Thomas’s suggestion that effective institutions will require the development of new “social technologies.”An emphasis on social technologies seemed to appeal to the commission and many of the presenters as a new frontier for promoting scientific innovation in a way that is safe, responsible, and democratically accountable without over-relying on top-down regulation.

More controversially, Buchanan clarified the meaning of “dual use” by subdividing it into two types. The more commonly understood form of dual use is the possibility that terrorist groups or rogue states could misuse a technology like synbio, but Buchanan also proposed that “good” actors or states could use synthetic biology for offensive purposes in the name of defending themselves. As an example, he pointed to the grossly unethical human radiation experiments perfumed by the U.S. government from 1944 to 1973.

Buchanan concluded by encouraging the commission to focus on these concrete risks and benefits and not get bogged down with more intrinsic unanswerable questions about human nature, the meaning of life, or the implications of biological materialism for human moral agency. He was clearly asking for the commission to be decisively pragmatic in its recommendations for managing the risks and benefits of synbio without completely ignoring various theoretical views and approaches.

During the audience Q & A period, Gerald Epstein of American Association for the Advancement of Science reminded the commission that synbio will only be one component of much larger issues that humanity faces and that and it should try to analyze the implications of synbio for social justice, human security, or the environment “as a whole.” These discussions moved the conversation toward an emphasis on concrete risks and benefits of synbio for a diverse and complex global environment.

The second day of the meeting continued to place synthetic biology in this broader context. Paul Wolpe of Emory University reminded the commission that humans create technology that then goes on to recreate human existence—examples of this range from the plow, to the car, to the Internet. He speculated on the numerous effects that synbio can have on human lifestyles and humankind’s conception of itself, but he eventually zeroed in on the contrast between the value that humans place on speed and the human impulse to respond to technology incrementally.

Synbio will increase the speed of various biological processes, but humans will only come to understand it incrementally, not realizing the transformative potential of the technology until it has actually transformed our lives. It is this fear of incremental steps toward an irrevocable transformation of human existence that has underpinned some of the behavior-based religious systems and even the “playing god” objection. Wolpe recommended that the commission address synbio in “a positive way by creating goals and incentives rather than trying to stop things.”

He also cautioned that this positive view of synbio’s capabilities be tempered with a wisdom that avoids fetishizing science by over-relying on arguments based on utopian visions or a hyperbolic sense of urgency. So, not only must the commission focus on managing concrete risks and benefits in a global environment, it must understand those risks and benefits in terms of the diverse cultural and religious values held by many of the world’s populations. The commission must also be humble enough to understand that common beliefs about the beneficent power of science and society’s ability to grapple with its implications as possessing their own biases and limitations.

This line of discussion made the meeting as a whole very productive. It elucidated many of the most compelling arguments for a positive, risk management-based, globally-contextualized, culturally self-aware, and pragmatic approach. By coupling this approach to the specific safety and oversight concerns of scientists, business leaders, government officials, and everyday citizens, the commission can find a way to be open to various views of scientific progress while also being critical of them as it makes concrete recommendations. This is what a bioethics commission should be doing, paving a confident path through the ethical forest while respecting the great variety of the trees.

Michael Rugnetta is a Research Assistant to Jonathan Moreno for the Center for American Progress’s Progressive Bioethics Initiative and Science Progress.

There are three major provisions in the new law that promise to bring care-enhancing innovations to patients everywhere. The Cures Acceleration Network, or CAN, will speed new therapies from bench to bedside. The Patient-Centered Outcomes Research Institute will bring develop and disseminate information on the effectiveness of different treatments. And the Qualifying Therapeutic Discovery Project Credit will support small biotech firms investing in new treatments for unmet and chronic care needs.

The goal of the Cures Acceleration Network, introduced by Sen. Arlen Specter (D-PA), is “to accelerate the development of high needs cures,” defined by the legislation as priority treatments “for which incentives of the commercial market are unlikely to result in adequate or timely development.” These therapies may include regenerative medicine treatments that rely on decoding genes and mapping complex biochemical pathways for diseases like Parkinson’s, ALS, or multiple sclerosis.

The new law authorizes $500 million for fiscal year 2010, allocated through grants or contracts that may not exceed $15 million. The contracts are termed “partnership awards” and require the recipient to contribute matching funds of one dollar for every three federal dollars, whereas the “grant awards” do not require a match. The National Institutes of Health director is also given the authority to dispense no more than 20 percent of the appropriated funds at his own discretion for “flexible awards.”

As well, another component of the Cures Acceleration Network mission will be to facilitate Food and Drug Administration review of these high-needs cures. The bill instructs the FDA to coordinate its approval requirements with CAN’s activities and to provide technical assistance in order to expedite product development and approval.

CAN will also promote personalized medicine by supporting the development of diagnostics, preventative therapies, and behavioral therapies, as well as biomarkers that can predict the safety and effectiveness of such therapies for patients based on their individual genetic makeup.

Senators Max Baucus (D-MT) and Kent Conrad (D-ND) originally introduced the Patient Centered Outcomes Research Institute last summer in separate legislation. I explained then that the project was “designed to ramp up medical innovation for the common good by championing a new era of personalized medicine.”

This Institute will be tasked with organizing, funding, aggregating, and disseminating comparative effectiveness research, which looks at two or more treatments side by side to see which produces better health outcomes for a particular group of patients. The version of the Institute enacted in the health reform bill will be established as a non-profit entity that is completely separate from the federal government. A dedicated tax stream will fund the Institute’s trust fund beginning in 2013, but the law also appropriates Treasury funds for the trust fund from 2010 until 2019, when both sources of funding sunset.

Research at the Institute will pay special attention to the needs of subpopulations including “racial and ethnic minorities, women, age, and groups of individuals with different comorbidities, genetic and molecular sub-types, or quality of life preferences.” It will explore the impact of where treatments are in the product development process and the skill level of health professionals administering the treatment to see how those factors impact effectiveness. These are real-world considerations that other forms of research like clinical trials often miss.

Most importantly, the Institute is charged with making its data comprehensible, protecting patient privacy and confidentiality, and explaining the data’s limitations and relevance for subpopulations. The Personalized Medicine Coalition, a non-profit representing a broad array of private, public, non-profit, and academic stakeholders has praised the bill’s establishment of the Institute and its thorough incorporation of personalized medicine.

The law also contains good news for small biotech companies, specifically those with less than 250 employees. These firms will be eligible for a tax credit equal to 50 percent of their investment in any “qualifying therapeutic discovery project.” These can include pre-clinical studies, clinical trials, or other clinical studies conducted for the purpose of winning FDA approval of a treatment, diagnostic, or treatment delivery technology. Companies will need to apply for these tax credits and the total amount may not exceed $1 billion for FYs 2009-2010. The projects must possess certain attributes, such as the potential to treat chronic conditions or ailments in areas of unmet need, reduce long-term health care costs, or contribute to curing cancer. The selected projects must also have “the greatest potential to create and sustain high quality, high-paying jobs.”

Another issue addressed by the law has to do with the biologics industry. Biologics are drugs composed of large, complex molecules that are manufactured through complicated cellular processes, as opposed to small-molecule drugs that are manufactured through simple chemical reactions. Since these drugs are so complex that a firm can create a generic version of an existing drug that is similar enough to fit into the same drug class but different enough to avoiding infringing the patent for the reference drug. These generics are referred to as “biosimilars” or “follow-on biologics.” The health reform law alters the landscape for biologics by establishing a clear FDA regulatory pathway for biosimilar drugs while simultaneously establishing a 12-year period of market exclusivity protection for the companies that create the original biologics. Early reports indicate that the new law seems positive for the biotech industry as a whole.

The legislation also leverages transparency efforts to reduce conflicts of interest within medical research and clinical practice. In 2013, the Department of Health and Human Services will begin tracking the funds and gifts that the medical industry provides to physicians, researchers, and hospitals through reporting requirements. This information will then be made available in a public database.

Michael Rugnetta is a research assistant with the Progressive Bioethics Initiative at the Center for American Progress.

The next day Oxford weather reverted to form, chilly and damp, but back home the world had changed. British colleagues, while offering congratulations, expressed their usual befuddled amusement at their old colonies’ reluctance to accept the notion of a decent public space. The Brits, of course, are soon to elect a new Parliament, and to the surprise of nearly everyone, the polls show that Labour might retain control, in spite of the massive unpopularity of the Brown government, worries about massive government debt, and a British Air strike ill-timed for Labour.

Even if the Tories pull it off one thing will not change. A couple of decades after Margaret Thatcher the National Health Service remains a popular institution. The welfare state that Churchill claimed was a “Gestapo” in the making is not in jeopardy more than 60 years on (though the tea partiers in the United States could well claim Churchill as their hero). Clement Attlee is not a world historical name, yet as prime minister he consolidated the social democracy that Brits wanted after the War. True, as one colleague observed at yet another pub meal, she was grateful to pay up for a private dentist when she needed a root canal, but no one at the table urged the end of the safety net NHS provides.

I was asked why Americans tend to look to the British way of providing health care when there are so many other models that are in many ways superior. The obvious answer is that we don’t speak French or German enough for them to be viable models, but in truth the Continental systems are both more highly rated for the health outcomes and more technologically advanced than the British. Whether we can “bend the curve” and control the rate at which health costs increase will depend to a great extent on science and technology. Systematic treatment comparisons will need to inform and guide health care decisions, even though outcomes data are often provisional. And the health reform legislation provides for just that in the form of a new institute that will study and compare the effectiveness of different clinical approaches. Information technology might someday improve those results but the platforms available now don’t seem to conform to the way doctors think or practice.

At the end of the day, however, at the current rate of expansion of our ability to intervene in an individual’s medical condition, no country will be able to afford “everything.” The ultimate approach to health care costs must be cultural and moral as well as technical: What do we owe each other?

Unless I have missed other news reports, U.S. conservative cries that the passage of health reform is socialism in the making have not yet turned either the Capitol or the House of Commons into the Kremlin. British democracy remains noisy, full of beans, with a raucous newspaper culture. From the British we can learn that a decent respect for the common good is not a form of tyranny. Perhaps we have taken the first step.

Jonathan D. Moreno, Ph.D., is the David and Lyn Silfen University Professor of Ethics and Professor of Medical Ethics and of the History and Sociology of Science at the University of Pennsylvania, and the Editor-in-Chief of Science Progress.

Much Promise and Many Questions

There are promising developments heralding the arrival of personalized medicine, a new medical field where the results of genetic tests or other biomarker assessments are used to tailor drugs and treatments to individual patients. A year ago, for example, the Food and Drug Administration approved maraviroc, the first drug designed specifically for HIV patients who have a particular genetic mutation of the virus. This was the first time a drug had been approved upon the condition that patients first have a genetic test.[1] Similarly, in July scientists at the Van Andel Research Institute published a paper reporting that high expression of the gene known as MET increases the aggressiveness of certain types of breast cancer. This means that the MET gene can be used as a target for new cancer therapies that may inhibit MET’s expression, thereby slowing down the most aggressive forms of breast cancer.[2]

In spite of this kind of progress on the scientific front, Americans today remain guinea pigs in a “one-size-fits-all” approach to medicine in which clinical trials to test the safety and efficacy of new drugs do not take into account the influence of individual genes on individual health and wellness. In contrast, a personalized medicine approach may well allow (perhaps in the not too distant future) every individual patient to receive the best in tailor-made, evidence-based pharmocogenomic medicine.

Similarly, research, development, and clinical care in our health care system merely ensure that medical treatments will work for most of the population most of the time. In fact, most drugs prescribed today only work in 60 percent of patients or less.[3] Personalized medicine promises that treatments will be tailored to individuals by researching the effects of specifically tailored treatments on genetic subpopulations. Since one size does not fit all, personalized medicine will represent a marked improvement over the current system where patients are left to travel down a winding path of physician-led trial and error.

Compounding the unwieldiness of today’s haphazard clinical approach is the disjointed health care informatics system that prevents scientists and physicians from making the most of our nation’s personalized genomics research data. Our impersonal and uncoordinated approach to care costs lives and squanders billions of dollars that could go towards insuring the 45 million Americans who are without coverage while also bringing down costs.[4]

In short, we are awash in evidence that not all individuals will respond similarly to the same medical treatment. But we have not taken the steps to integrate personalized medicine fully into our health care system in order to benefit individuals and society alike.

Granted, there is still a lot we don’t know, especially when it comes to genetics. Most of the genes that have been discovered only have small effects from a diagnostic perspective.[5] But, the bigger question is how can scientists who are eager to expedite the integration of personalized medicine into clinical practice efficiently gather and disseminate their discoveries? It is because of this question that we should look at personalized medicine as contributing to the ultimate goal of turning medical practice into a total learning environment. This means physicians would be able to apply the most recent findings about the efficacy of available treatments while also sharing the outcomes of their own treatment decisions with others so that all physicians can have better data the next time around. This information will also be available to academic scientists and industry researchers so that they can gear their research and product development in more patient-specific directions.

Of course, given the private interests of all the various stakeholders involved, it should be no surprise that bringing about the era of personalized medicine will be no easy task. Many lingering legal, political, and administrative questions remain about patient privacy and about the ownership, organization, and security of the data. And those are just the tip of the iceberg when one considers the vast technical difficulties that computer programmers and health technologists are trying to overcome.

In April, at the Bio-IT World Conference and Exposition in Boston, for example, Microsoft Corp. announced the coming release of Amalga Life Sciences, which promises to be a single platform for aggregating and modeling data from “basic research, clinical trials, health care delivery, and consumer health information needs.”[6] Amalga will also be linked to Microsoft HealthVault so that patients can import their medical data generated at the hospital into their own personal health file.[7] This is an ambitious project that will need to be watched closely in action to see if it enhances or limits the ability of physicians, researchers, and patients to access the information they need in a way that is useful, understandable, and comfortable for them.

For now, though, the bottom line is that there definitely needs to be a strong public debate about what health information is going to look like and what it is going to do. The most promising way to begin this debate is to not get bogged down in the technical questions just yet. Instead, this is a ripe time for taking stock in what values should guide our vision of personalized medicine; what tools we already have available to bring it about; and how responsibilities should be divided up or combined by public and private stakeholders.

Some federal government entities have already started taking steps to answer these questions by moving ahead with initiatives that better streamline the data, technology, and research efforts that are already available. The National Institutes of Health, for example, announced in February that it is moving forward on a clinical trial that will test the effectiveness of integrating genetic data into the dosing protocol for the blood-thinning drug warfarin. This happened just weeks after then-acting Director of the Food and Drug Administration Frank Torti announced that the FDA created a new position in the Office of the Chief Scientist called Senior Genomics Advisor. This office has been filled by FDA veteran Dr. Liz Mansfield, whose job will be to provide “FDA physicians and scientists with tools and personnel capable of high-level analysis of complex genetic data.”[8]

Taking a broader view, the Personalized Healthcare Initiative in the Department of Health and Human Service’s Office of the Assistant Secretary for Planning and Evaluation has conducted reviews of current federal efforts in order to identify organizational challenges to achieving overarching goals. This PHC initiative highlights the need for connecting clinical records with genomic information, ensuring the integrity and privacy of genetic data, preventing discrimination, ensuring the accuracy and validity of genetic tests, and devising common access protocols for genomic databases.

The PHC initiative also highlights various tasks for many government agencies and programs to ensure that that they do their part to achieve these goals for the ethical and coordinated advancement of personalized healthcare. Some of these tasks include directing other agencies in Health and Human Services to devise ways for sharing their data so that the genomic, clinical, and public health aspects of personalized medicine can mutually reinforce one another rather than remain siloed and even redundant in their research and analyses. The PHC initiative also includes in its review the ethical analyses published by the HHS Secretary’s Advisory Committee for Genetics, Health, and Society, or SACGHS, on large-population genetic studies and the bureaucratic logistics of pharmacogenomic research.[9]

Other principled concerns about personalized medicine have also been addressed in general terms through SACGHS, a permanent group that advises the secretary on, among other things, personalized medicine and occasionally releases reports on the issues at hand.[10] Yet the fine practical details of these concerns still need to be hashed out by multiple collaborators on a case-by-case basis.

These concerns have to do with the inclusion of private entities in data-sharing about the validity, utility, and effectiveness of various technologies. What should private biotech companies, pharmaceutical companies, or diagnostic companies be required to share with the federal government? A recent SACGHS report recommends:

In situations where tests are essential to clinical drug use, HHS should require its
grantees and contractors to participate in FDA’s Voluntary Genomic Data Submission Program during the exploratory phase of drug development and/or the review process
for preinvestigational device exemption.[11]

This FDA program is overseen by a body known as the Interdisciplinary Pharmacogenomics Review Group, which was charged in 2005 with collecting phramacogenomic data about drugs in the developmental stage. This program has made regulators more cognizant of genomics, has influenced discussions on clinical trial design, and has even led to the development of a pilot process for qualification of biomarkers for use in regulatory decisions.[12]

From the standpoint of trying to better integrate pharmacogenomic data into the drug development process, this is a great idea. And personalized medicine would advance even more rapidly if pharmaceutical companies could cost-effectively collect information from large-cohort genetic studies and use that information to design better-targeted and more information-rich clinical trials. But companies are reluctant to invest more money in doing their own large-population-based genetic studies that may or may not help them to make a better product let alone recoup their investment.

So who pays for these large-population genetic studies? Usually, it is the NIH. But how can NIH orient its genetic research toward personalizing the drugs that the private sector is developing? SACGHS recommends that the recipients of NIH grants for research that “will be used to demonstrate safety and efficacy to support a [drug or device’s] premarket review application” to the FDA should consult with FDA “early in the study design phase.”[13] Again, this is a practical idea but there needs to be a concerted effort on the part of HHS to make this cooperation materialize on a case-by-case basis.

As pharmacogenomic research develops methodologically and as further evidence is gathered about the application of pharmacogenomic technologies in clinical practice, the policies and protocols for public/private collaboration will need to develop as well. For instance, the SACGHS report makes recommendations about stratifying subject populations based on their predispositions to adverse reactions as indicated by their biomarkers. These recommendations include having the FDA guide the collection of genetic and biological factors that are better predictors of drug responses than race, ethnicity, or gender; and having post-market follow up to find other biological, social, or environmental factors that influence drug response when there is a racial or ethnic disparity in drug response.[14]

Other examples include the plethora of recommendations that SACGHS makes concerning the increasingly controversial areas of insurance coverage and reimbursement, clinical practice guidelines, professional certification, and drug labeling.[15] What we know so far is that these are all relevant issues that can be dealt with by means of better coordination throughout the entire healthcare system.

Researchers need to be informed of all the relevant data collection initiatives. Regulators need to be better aware of the technologies that are coming down the pike. Corporations need to engage in partnerships with the public sector in order to share data for the public good and develop more personalized drugs. And, the FDA needs to encourage drug and device companies to do post-market follow up and coordinate it with the development of new products.

There also needs to be coordination between the genetic test manufacturers, the drug manufacturers, and the health care providers who need to gather evidence for them as they implement tests and therapies in the clinic. The problem, however, is that we do not have sufficient knowledge—both in terms of biomedical data and real-world policy experience—to set in stone any policies for systemic coordination on personalized medicine just yet.[16] Therefore, the best course of action for the time being is for HHS to emphasize better coordination in general, and to guide various coordinated projects by holding them accountable to the broad goals and values put forth in the SACGHS reports and in the work done by the PHC initiative.

This might be a job for HHS’s Office of the Assistant Secretary for Planning and Evaluation, which could:

• Consult with various agencies, programs, and private entities
• Suggest opportunities for collaboration
• Help to iron the terms on which these entities do collaborate

As various personalized medicine initiatives are implemented, HHS can then look at the protocols and policies that do and do not work in terms of data sharing, research coordination, or product development.

This would create an iterative self-correcting process that would allow us to gather more data on personal genomics and conduct more research into the implementation of personalized medicine. Thus, the United States will rapidly build a knowledge base for the future of personalized medicine while it still takes the time to learn how to develop the right policies for shaping that future.

Indeed, all of the initiatives described above are promising steps toward the development of personalized medicine as a new paradigm for medical practice. Nevertheless, the United States still has a long way to go before personalized genomics becomes a standard part of medical practice. Implementation and evaluation must proceed aggressively in tandem in order for us to not only achieve a personalized medicine revolution speedily, but also achieve it efficiently and ethically. This is the essence of progressive innovation and pragmatic policy making. For personalized medicine to fully come to fruition with the fewest number of bumps in the road, we must learn valuable lessons from the current piece-by-piece process as we ramp up our efforts to build upon it.

About the Authors

Michael Rugnetta is a Research Assistant with the Progressive Bioethics Initiative at the Center for American Progress and Whitney Kramer is an intern working on the Progressive Bioethics Initiative.

Endnotes

[1] “Virus-specific Drug Approved for HIV,” New Scientist, August 11, 2007, available at http://www.newscientist.com/article/dn12456-virusspecific-drug-approved-for-hiv.html.

[2] “Possible Drug Target Found For One Of The Most Aggressive Breast Cancers,” Science Daily, July 9, 2009, available at http://www.sciencedaily.com/releases/2009/07/090708153238.htm.

[3] Federal Coordinating Council for Comparative Effectiveness Research, Report to the President and the Congress, (Health and Human Services, 2009) available at http://www.hhs.gov/recovery/programs/cer/cerannualrpt.pdf.

[4] Paul Ginsberg, “Efficiency and Quality: The Role of Controlling Health Care Cost Growth in Health Care Reform,” (Washington: Center for American Progress, 2009) available at http://www.americanprogress.org/issues/2009/06/payment_reform.html.

[5] Alan M. Garber and Sean R. Tunis, “Does Comparative-Effectiveness Research Threaten Personalized Medicine?” New England Journal of Medicine 360 (19) (2009): 1925-1927.

[6] John Russell, “Microsoft Launches Amalga Life Sciences,” Bio-IT World, April 28, 2009, available at http://www.bio-itworld.com/news/2009/04/28/amalgals.html.

[7] Microsoft, “Microsoft Introduces Next-Generation Amalga Unified Intelligence System,” Press release, April 6, 2009, available at http://www.microsoft.com/presspass/press/2009/apr09/04-06AmalgaUISPR.mspx.

[8] U.S. Food and Drug Administration, “Viewpoint: FDA and Genomics,” February 2, 2009, available at http://www.fda.gov/AboutFDA/CommissionersPage/Viewpoint/Archives/ucm153614.htm.

[9] Health and Human Services, “Personalized Health Care,” available at http://www.hhs.gov/myhealthcare/.

[10] Office of Biotechnology Activities, “Secretary’s Advisory Committee on Genetics, Health, and Society,” available at http://oba.od.nih.gov/sacghs/sacghs_home.html.

[11] Advisory Committee on Genetics, Health, and Society, “Realizing the Potential of Pharmacogenomics: Opportunities and Challenges; A Report of the Secretary’s Advisory Committee on Genetics, Health, and Society,” (Health and Human Services, 2008) p. 24, available at http://oba.od.nih.gov/oba/SACGHS/reports/SACGHS_PGx_report.pdf.

[12] U.S. Food and Drug Administration, “Interdisciplinary Pharmacogenomics Review Group,” available at http://www.fda.gov/Drugs/ScienceResearch/ResearchAreas/Pharmacogenetics/ucm083889.htm.

[13] Advisory Committee on Genetics, Health, and Society, “Realizing the Potential of Pharmacogenomics: Opportunities and Challenges; A Report of the Secretary’s Advisory Committee on Genetics, Health, and Society,” (Health and Human Services, 2008) p. 24, available at http://oba.od.nih.gov/oba/SACGHS/reports/SACGHS_PGx_report.pdf.

[14] Advisory Committee on Genetics, Health, and Society, “Realizing the Potential of Pharmacogenomics: Opportunities and Challenges; A Report of the Secretary’s Advisory Committee on Genetics, Health, and Society,” (Health and Human Services, 2008) p. 43, available at http://oba.od.nih.gov/oba/SACGHS/reports/SACGHS_PGx_report.pdf.

[15] Advisory Committee on Genetics, Health, and Society, “Realizing the Potential of Pharmacogenomics: Opportunities and Challenges; A Report of the Secretary’s Advisory Committee on Genetics, Health, and Society,” (Health and Human Services, 2008) p. 4-8, available at http://oba.od.nih.gov/oba/SACGHS/reports/SACGHS_PGx_report.pdf.

[16] Alan M. Garber and Sean R. Tunis “Does Comparative-Effectiveness Research Threaten Personalized Medicine?” New England Journal of Medicine 360 (19) (2009): 1925-1927.

That none of this is true seems almost beside the point. Americans are getting nervous and that is not good news for health care reform. Supporters of reform are now working overtime to reassure us that health care reform will not make us worse off, that it will instead improve the quality of the care we get, and that if we like what we have, we can keep it. Health care reform will not change, in any way that matters to us, the self-interested world we each inhabit.

At the risk of sounding like a Pollyanna, we want to try a different tack. Each of us should support health care reform because it is the right thing to do.

We should say at the outset that although we do ethics for a living, we are neither impartial nor indifferent to the needs of those we love. When someone in our families is ill, we do every thing in our power to get them every medical intervention whose benefits outweigh the harms. We desperately want them to have the best. And because we have excellent employer-sponsored insurance, and have the resources to pay for whatever out of pocket costs there might be, we usually succeed.

But we are always painfully aware that what we can do for our families, many other people cannot. And we are also aware that there is no morally defensible reason why we are in this position and they are not. Our system is just unfair.

Most of us who have insurance—whether through our employers or through Medicare—do so because the government pays a big chunk of the bill. Most of us who don’t have insurance don’t qualify for the tax breaks that go along with employer-sponsored health insurance and are just too young for Medicare.

Not that insurance insulates a family from the staggering financial burdens of a serious illness. If you are happy with your health insurance it may be because no one in your family has ever had advanced cancer, serious arthritis, a debilitating brain accident, or any number of illnesses or injuries where the cost of care can exceed by tens of thousands of dollars a year your insurance benefits. Putting aside the contentious issue of whether those wealthy enough to absorb such costs deserve to be that much better off, surely in a country as rich as ours no family should have to be in the awful position of being unable to secure critical medical care because they cannot afford it.

So what does this have to do with a personal moral responsibility to support health care reform? We each have a duty to take care of our loved ones and that extends, of course, to making sure that what is good and valuable about the health care they now have is preserved. But don’t be misled into thinking you are being asked to trade away your family’s interests. The next time you hear how health care reform is going to get between you and your doctor or deny you needed care, press for specifics. Despite the hype, the proposals currently being debated in Congress impose minimal or no burdens on most of us. Indeed, we will be more secure with health care reform than we are now. After all, while we may be healthy or have good insurance today, that may not be the case tomorrow.

But even if, in the near term, some of us may be slightly worse off than we are today, there is a line between appropriate self interest and simple selfishness. Opposing health care reform crosses that line.

This is a case where we can have our moral cake and eat it too. In supporting health care reform, we can be good citizens and morally responsible neighbors, and still do right by those we love. We want a country in which all families, not just ours, have affordable, high quality health care. Don’t you?

Ruth R. Faden is the Wagley Professor of Biomedical Ethics and Director of the Johns Hopkins Berman Institute of Bioethics. Jonathan D. Moreno is the Silfen University Professor of Medical Ethics at the University of Pennsylvania and a Senior Fellow at the Center for American Progress.

Her hook is the quest of Amy Farber, who found out in 2005 that she had LAM, a rare and fatal disease affecting women that damages respiration and destroys a variety of bodily systems over time. Farber teamed up with George Demitri of Harvard Medical School and Frank Moss, director of the MIT Media Lab and the lab’s New Media Medicine group.

The result was LAMsight, a project that brings together patients from around the world who share knowledge and experience with doctors and researchers who can sift through that information to improve their understanding of the disease. Some of the people with the most knowledge of LAM are of course the patients, and the network can facilitate their access to clinical trials as treatments evolve. The effort brings patients in as collaborators in health research:

Patients’ everyday experiences in living with an illness are an enormous source of untapped data, [Moss] said; aggregated, those data could generate new hypotheses and avenues for research. “We’re really turning patients into scientists and changing the balance of power between clinicians and scientists and patients,” he said.

The site allows participants to remain entirely anonymous to other users if they so choose, but the article of course raises the issue of privacy concerns that surround many new web-enabled health projects, as well as the quality of data provided by small self-selecting communities.

In the case of LAMsight, participants are making an active decision to become a research participant. But Arnquist also points to commercial ventures such as 23andMe and PatientsLikeMe that are actively recruiting consumers to share genetic and health information that populates databases that may also prove useful for studying an array of health issues.

Stanford bioethicist Sandra Lee, who recently spoke with SP about direct-to-consumer genetic testing, discussed the policy tensions such DTC services create. On the one hand, they allow people who want to actively participate in research (or become scientists, as Moss might suggest) to do so—an empowering and potentially beneficial engagement with their health. On the other hand, some of those people may become unwitting research subjects, and the genetic information they share, Lee notes, is not just about them, but by virtue of familial bonds, is also about others who might not have consented to share that information with others.

The point of course is not to restrict health or genetic information sharing unnecessarily, but to finesse the balance for individual projects; protect privacy, safety, and autonomy; and create more hope for more patients.

Payment reform will be a catalyst to transform our broken health care system, but without a more well-rounded health information technology strategy-efforts to date have focused chiefly on the adoption of electronic medical records-health care providers will not have all the tools to truly move to the population-based, health-oriented system that current policymakers envision. Similarly, to move our society to a truly health-oriented culture some fundamental cultural shifts will need to occur. Health information technology can help move that needle, too.

In essence, HIT policy initiatives must be far broader if we are to succeed in fixing healthcare. The key to solving the cost and quality dilemma is to employ strategies that involve patients more in their health care decision making. The idea is to give them as much opportunity to make their own health care decisions regarding wellness and prevention and, along with their doctors, make medical decisions. To help patients do this they need information technology to monitor their own health and “health coaches” armed with the same health monitoring information.

Health care providers today are a scarce commodity and expensive labor, especially when patients usually visit them only after symptoms prompt them to seek medical help. A strategy focused on the adoption of electronic medical records by physicians will not achieve the goal of bringing patients fully into the decision-making process about overall healthy living. For that, another set of tools is required.

We at the Partners Healthcare System in Boston call this set of tools “connected health.” Connected health involves the use of technologies, which predominantly involve messaging and monitoring, to accomplish two broad goals:

• Extend care to patients where they are when they need it
• Give patients the tools that enable them to be their own primary care provider whenever possible, with the help of a health coach.

The conditions that best fit this approach initially are chronic illnesses such as hypertension, diabetes, and asthma. The choice is strategic-these conditions represent the fastest-growing segment of health care demand and account for much of health care costs. Our system applies four core principles in designing connected health programs for these conditions:

• Gather accurate information such as vital signs, adherence to a wellness plan, and certain behaviors.
• Share that information with patients in a context they can relate to.
• Provide coaching based on how patients are performing relative to the information that is tracked, with coaches having access to the same data as the patient.
• Provide the health care provider with only the information required to make the best care decision.

An example of our approach is the hypertension self-management program that our Center for Connected Health studied in collaboration with the data storage company EMC Corp. Employees at EMC were enrolled based on their blood pressure readings at a hypertension screening. The intervention was a blood pressure cuff for home or workplace blood pressure monitoring, a device to get the readings out of the cuff and onto the Internet, and a rich website that the employee used to see blood pressure trends and access educational materials. The site was also customized with automated coaching messages that were determined by the employee’s health status and blood pressure trends.

The results after six months were striking. Less than 1 percent of enrollees dropped out. They uploaded an average of three blood pressure readings per week and logged onto the Website an average of once per week for the duration of the study. Most importantly, the blood pressure readings in the intervention group were significantly lower than those in the control group. This service is now being offered by the Center to other employers as a tool to engage employees in healthier behaviors and lower overall costs of care.

There are many more examples of this approach. We are having great success, for instance, with a diabetes program that allows a nurse clinician to follow the blood glucose readings of a panel of patients and intervene just in time if their readings are out of control. In a way, connected health is the logical, patient-facing extension of the electronic record or the next generation of health information technology.

One stumbling block to implementing this vision is the current predominant reimbursement model of fee for service. In this context, there is really no incentive for health care providers to provide lower-cost care. Units of service drive revenue so workflows and strategies are naturally employed that drive more services per unit time.

The Obama administration’s insistence on coupling payment reform with access reform is laudable. The predominant payment models being discussed at this time are bundled payments, where providers are paid a flat fee for a given condition set for a unit of time, and shared savings where providers are paid a management fee (much as health plans are) and agree to achieve savings goals. These strategies are sometimes described under the banner heading “value-based purchasing.”

Both of these payment models reward health care providers for the quality of outcomes rather than units of service. Our experience at the Center for Connected Health tells us that when confronted with this type of payment scenario, connected health tools are a compelling way to achieve improved population health and efficiency.

Our experience and success to date with connected health are all with the segment of the population that will willingly come forward to participate in this type of program. They are willing to be constantly fed unambiguous health data over the Internet and agree to share that data with their physicians and their health coaches.

But what about those who find engaging in healthy behaviors to be especially challenging? We have some preliminary data at the Center for Connected Health that suggests this group, in general, has worse health outcomes than those who will be part of a connected health program that is likely to emerge in some fashion out of the deliberations now proceeding in Congress. Case in point: We followed heart failure patients on discharge from the hospital. Half were offered participation in a telemonitoring program and half were offered usual care. Of the half offered the program, those who refused to participate had worse outcomes than the control group.

Our sense is that tools such as incentives and other behavioral economic tools will be required to bring this group in. One thing we’ve noticed: once patients are involved in a connected health program their persistence is high. Drop outs are rare.

At the Center for Connected Health we have generated solid data and significant clinical experience to demonstrate that our initiatives to connect patients and physicians can effectively improve outcomes, reduce costs and more effectively manage healthcare resources. As it turns out, our connected health programs can be quite robust and exciting for patients of all age and income groups, as well as for providers, payers and employers. As such, we view connected health as an integral solution in a healthcare reform package, to ensure quality, affordable healthcare for all Americans.

Joseph C. Kvedar, MD, is founder and director of the Center for Connected Health at Partners HealthCare System in Boston, Massachusetts.

But today the Associated Press has a story on the newly digitized Children’s Hospital of Pittsburgh that presents a clear narrative of how computer-powered records work in real life, speeding diagnoses, preventing costly and dangerous errors, and helping administrators track effective techniques.

The boon to patient care and hospital bottom lines are compelling reasons to move to EHRs. The power to keep young children healthy is a good one too.

See also: Data Bank: Health Information Technology

More from CAP: “A Historic Opportunity: Wedding Health Information Technology to Care Delivery Innovation and Provider Payment Reform”

(HT: Kaiser Health News)

The bill would provide the Food and Drug Administration with unprecedented control over the tobacco industry. This act allows FDA to require full disclosure of ingredient lists and to order tobacco companies to reduce the amount of harmful ingredients in their products. It would also change warning label content and increase label size, as well as ban marketing to minors. The Secretary of Health and Human Services reserves the authority to mandate additional changes to warning labels that benefit public health. The legislation also prohibits labeling cigarette packets with phrases like “light” and “low tar,” which are often deceiving to consumers and mask the health risks. It would also forbid the sale of most flavored cigarettes.

For the moment, cigarettes remain unregulated drug delivery systems. Here’s a look at some of the most recent data on national smoking trends:

19.8 percent of adults in the United States (43.4 million people) were current smokers in 2007.

30 percent of all cancer deaths involve smoking as the primary cause.

443,000 people died prematurely every year as a result of smoking and exposure to tobacco smoke during the period between 2000 and 2004.

During that same period, smoking caused $98 billion in productivity losses each year.

For every person who dies of a smoking-related disease, 20 more people suffer with at least one serious illness from smoking.

20 percent of high school students were smokers in 2007.

3,600 people between the ages of 12 and 17 pick up smoking everyday.

Image: flickr user Sami__

These new studies will also allow health care providers to make the best decisions about the range of available options for treating patients. Without them, providers may have to rely on information from a drug maker or medical device company that has a financial interest in promoting a particular remedy. Comparative effectiveness research, Ruth Faden explains, “Is a very simple concept with a very fancy term.”

Professor Faden is the executive director of the Johns Hopkins Berman Institute of Bioethics and a Philip Franklin Wagley Professor in Biomedical Ethics at Johns Hopkins University, and she discusses the issue—its basic goals, benefits, and how the United Kingdom uses it in its country’s health system—with CAP senior fellow Jonathan D. Moreno in this new Science Progress podcast. To listen, see the audio player in the sidebar, download the mp3, or subscribe via iTunes.

The basic idea behind the research is to form a direct comparison of existing interventions for one illness—which could include different diagnostic techniques, courses of therapy, medications, and surgeries, as Faden said in her discussion with Moreno. The comparison helps researchers determine which treatments produce the best outcomes for different groups of patients. “Part of the trick is trying to figure out what works for whom. Clearly medicine doesn’t work in a one-size-fits-all frame of mind,” Faden said.

She also points out that comparative effectiveness is distinct from cost effectiveness. Cost effectiveness research attempts to determine the value derived from money invested in an intervention and is not necessarily coupled with comparative effectiveness research. While cost effectiveness aims solely to reduce costs, comparative effectiveness aims to decrease the number of mistreated patients as well as the number of patients who take longer to rehabilitate with treatment A when they could have recovered sooner with treatment B, Faden explained.

“We have to acknowledge that sometimes people go into the hospital and they get set back rather than improved in terms of their health. In some cases that’s because of accidents or errors; in other cases that’s because we just don’t know that something’s going to be harmful for a particular kind of patient. We expect fewer people to be harmed by the medical care they receive,” Faden said. In a broader sense, using this research will improve the quality of health care and decrease costs, as fewer patients will require multiple treatments for the same illness.

One example of how comparative effectiveness research has already proven useful is in the case of the common blood thinner drug, warfarin. Research indicated that depending on a heart patient’s age, one approach to treatment with the drug was more effective than another. This was important because improper dosing of the blood thinner poses serious risks. “If you didn’t aggregate by age or even by gender, then you wouldn’t know which approach would be best for which patient,” Faden said, referring to the warfarin dosing studies.

She also hopes that the information from comparative effectiveness research will be available to patients, especially as they get more involved in their medical decisions. Moreno and Faden co-authored an op-ed on the issue last month in the Baltimore Sun. They highlighted the power of the research: “Comparative effectiveness would allow patients and doctors to make decisions together based on the best possible scientific evidence, giving patients real choices based on solid information. An uninformed choice is like no choice at all.”

Researchers may take two different approaches to investigating evidence-based medicine. They can generate new data to create the direct comparisons, or they could synthesize groups of existing data on intervention use, Faden said. Both options are expensive, but designing new studies is especially costly. Although the $1 billion set aside in the ARRA may seem like a large amount of money, the research is necessary since “the payoff is tremendous,” Faden said. She continued: “Right now it’s sort of the orphan of clinical and biomedical research because it is so practical.”

While the United States is getting its bearings in comparative effectiveness research, the approach is already in motion in the U.K.’s National Institute for Clinical Excellence. NICE is connected to the National Health Service, the U.K.’s health care system. The goal of NICE is to establish values for investments made to maximize health outcomes, Faden explained. The institute strives to unify practice patterns that vary between England and Wales, and its research identifies the most effective treatments to help determine which drugs should be covered by the NHS’s universal entitlement program. Faden pointed out that despite the appeal of reducing health costs with comparative effectiveness research, NICE was partly established to help increase the access to more expensive treatments that were not necessarily available to all citizens and improve overall health and clinical practices in the U.K. One aspect of the NICE programs that people do not appreciate, she explained, “is that it was expressly set up to increase the uptake of certain expensive interventions in the U.K., particularly cancer drugs.”

Faden and Moreno forecast that the United States will be see an increase in comparative effectiveness research within the next couple of years, and that we should expect to know more about the efficacy of interventions we currently use in about five years.

Jonathan Moreno hosts this podcast; Science Progress intern Vivian Cheng produced it for the web.

Congress will provide the TRND program with $24 million a year for five years to conduct preclinical research and work on product development for rare and neglected diseases. If a drug survives the preclinical stage, TRND will contract a company to test the treatment clinically. These funds come from the $10.4 billion the NIH received from the stimulus package, intended to be spent by September 2010.

The NIH is targeting these diseases because private companies avoid this small market with little profit appeal, leaving patients with no treatment options. Only about 200 rare diseases have effective treatments today, as there are high barriers of entry for the pharmaceutical industry. Studies estimate that a potential drug requires between 8 and 15 years and upwards of $800 million to develop a new drug and introduce it to the market. The preclinical process, a focus of the TRND program, is the most difficult hurdle, costing $10 million and between two to four years itself. Without a successful preclinical stage, a treatment only has a 10 to 20 percent chance of reaching clinical trials, hence the nickname for this period, the “Valley of Death.” The NIH plans to use its funding and in-house academic resources to ease this process. The program will also address the difficulties in working with rare diseases, such as recruiting enough clinical trial patients, by partnering researchers with patient advocacy organizations and disease-oriented foundations.

The National Organization for Rare Disorders keeps a current database of rare diseases and associated organizations.

Image: AP/Marcio Jose Sanchez

Here’s a look at some of the numbers on how health IT can improve health care for all Americans by providing better quality and value.

Current spending on health is enormous:

16 percent of the U.S. gross domestic product currently goes toward health care spending.

20 percent of the U.S. gross domestic product will go toward health care spending in 2016, according to current predictions.

Health information technology can help prevent avoidable problems through better information coordination:

Every year, 100,000 people die in the United States as a result of preventable medical errors

There are 1.5 million annual preventable adverse drug events in the United States.

Without the widespread adoption of health IT systems, it will be impossible to implement value-based payment regimes for U.S. health care. Support from the American Recovery and Reinvestment Act’s HITECH can help spur adoption and meaningful use:

Only 13 percent of physicians currently use even a basic electronic health record, or EHR.

A mere 4 percent of physicians use a “fully functional” EHR.

1.5 percent of hospitals responding to a recent survey published in the New England of Medicine have a comprehensive electronic-records system.

8 to 12 percent of hospitals responding to the same survey have a basic electronic records system.

How the HITECH program can help:

$19 billion: the federal investment in the health IT authorized for the program.

74 percent: the proportion of hospitals responding to recent survey published in the New England Journal of Medicine citing inadequate capital as a primary barrier to adoption of health IT systems.

$44,000 to $64,000: amount of bonuses available under the program for health care providers who can demonstrate “meaningful use of certified EHRs.”

$11 million: bonuses paid through the system to hospitals  who can demonstrate “meaningful use of certified EHRs.”

Health IT can dramatically improve chronic care, which consumes massive portions of health-related spending in this country:

75 percent: proportion of all health spending that goes to treat chronic diseases such as diabetes, hypertension, heart disease, stroke, cancer, pulmonary conditions, and mental disorders.

56 percent: proportion of chronic care in the United States that appropriately involves evidence-based management.

125 million: the number of people in the United States suffering from at least one chronic care condition, as of the year 2000.

Read the full report, “A Historic Opportunity: Wedding Health Information Technology to Care Delivery Innovation and Provider Payment Reform” at the main CAP website.

Image: AP/John Raoux

But the Centers for Medicare and Medicaid Services recently released their “Proposed Decision Memo for Pharmacogenomic Testing for Warfarin Response,” in which they write that genetic testing does not improve “health outcomes in Medicare beneficiaries” when trying to predict responsiveness to the anticoagulant.

However, CMS did decide to pursue a strategy known as “coverage with evidence development,” which is authorized under the Social Security Act. This means that CMS will cover the cost of genetic tests for warfarin responsiveness if they are a part of a “prospective, randomized, controlled clinical trial.” In short, CMS will cover more research on use of the genetic test, but not pay for it in clinical settings.

According to GenomeWeb, private insures such as Aetna have also chosen not to cover the tests and have not been moved by the CMS decision to cover them for clinical trials.

Overall, this is a sensible policy and CMS lays out clear reasoning for it. Out of the six professional societies that provided their positions on pharmacogenomic testing for warfarin dosing, only two, the American Association for Clinical Chemistry and the College of American Pathologists, felt that there was sufficient evidence of effectiveness to warrant coverage. CMS also incorporated five expert opinions into their decision, all of which attested that the evidence regarding real-world health outcomes was insufficient. Michael Brophy of the Department of Veterans Affairs Diagnostic Services wrote that the genetic factors influencing response to the drug did not make a practical difference in clinical situations: “It’s only one of many factors that determine the appropriate dose.”

This decision is likewise important because it answers questions raised at a Medicare Evidence Development and Coverage Advisory Committee meeting in February on diagnostic genetic testing, which tests for diseases or anticipates drug response in patients. Most of the committee members felt that diagnostic genetic testing should be held to similar standards and criteria as other forms of diagnostic testing. The committee also emphasized that in order to assess the impact of diagnostic genetic testing on patient-centered health outcomes, there need to be “methodologically rigorous” evidence gathered on direct patient-centered health outcomes such as “mortality, functional status, and adverse events.”

If anything, these evaluations all to point to the need for robust evidence gathering. Personalized medicine will further require a sophisticated infrastructure for collecting, analyzing, and coordinating clinical and research information, and that necessitates investment in health information technology and comparative effectiveness research to reduce costs and improve health care outcomes.

And I haven’t mentioned the amputation of her right arm at age 39 due to a sarcoma, or the fact that she taught herself to drive and sew with one arm, or that she re-read all of Proust in French two years ago, or that she is a world-famous psychotherapist who still works and still writes. The memoirs will be published next year. I challenge anyone reading this to find a tougher or more independent nonagenarian than my mother. My wife and daughter find her a formidable feminist act to follow.

My mother was luckier than the president’s grandmother. She did not have any other serious disease and recouped her strength following each of her hip surgeries. So when I read the president’s thoughtful remarks about the question of whether someone in his grandmother’s or my mother’s position should be able to elect hip replacement in their eighties, I thought it important to tell her story. As the president indicated, there are tough choices ahead. Perhaps not all expensive procedures can be justified for those near the end of life, but not everyone in their eighties is near the end. We don’t have enough data to justify the level of confidence that close cases require, which is why the president is right to support research that compares the effectiveness of medical treatments, and speeding the implementation of computerized information systems for better coordination of care. It’s not for government to decide life’s up at 80, but eighty-year-olds, like amputees who are decades younger, need evidence to make choices, with their doctors and their families.

Now you might suppose that my mother would join the chorus of critics of the administration’s efforts to secure adequate health care for all Americans, fearful that someone like her might someday be denied one hip surgery, let alone three. But if you spoke with her you would find that, like most Americans, she believes that a decent society should provide care as a moral imperative, and that markets alone are not well-suited to address the vulnerabilities that can come with illness, especially for those without family and resources. She would tell you that Medicare isn’t perfect, but at least the government doesn’t spend up to a third of her premium on advertising. How much better would it be if our health care system demanded a high quality of care rather than just paying for more procedures?

So she will not be cowed by the cries of “rationing” we will surely hear in the next few weeks from certain self-interested parties, anymore than losing her arm or her hip intimidated her. Smart government can and must deliver a reasoned, evidence-based health plan for all. Compassion demands it. Is that so much to ask for Mother’s Day?

Jonathan D. Moreno is the David and Lyn Silfen University Professor of Ethics at the University of Pennsylvania, a Senior Fellow at the Center for American Progress, and the Editor-in-Chief of Science Progress.

NIH’s Pharmacogenomics Research Network has compiled data from 5,700 patients across the globe who are being prescribed the widely-used blood-thinning drug. Every year, 2 million Americans with certain heart conditions start taking warfarin, but their doctors often encounter difficulty with prescribing the drug since the optimal dosage for each individual patient varies widely. This usually results in doctors taking a trial-and-error approach to dosing that takes months to perfect and runs the risk of causing harmful side effects in the meantime. Warfarin is especially risky for patients for whom the optimal dosage is either very high or very low.

The patient data collected by the NIH included both the patients’ demographic and clinical information as well as genetic information on two gene variants, CYP2C9 and VKORC1, both of which are known to influence a patient’s ability to metabolize warfarin. The consortium also collected data on the initial and optimized doses of warfarin that the patients were prescribed.

According to an article published by the consortium in the New England Journal of Medicine, the 5,700 subjects were divided into two groups along an 80/20 split. This means the data for 80 percent of the subjects were used to construct a dosing algorithm and the other 20 percent were used as a validation cohort to test the algorithm. After running some statistical analyses, the researchers discovered that the addition of the genetic data to the demographic and clinical data allowed for a better prediction of the optimal dosage than just the demographic and clinical data alone. The genetic data was most helpful for those patients whose optimal doses are outside the average range—either very high or very low. This led an accompanying editorial in NEJM by Janet Woodcock and Lawrence Lesko of the Center for Drug Evaluation and Research at the FDA to argue that for warfarin, the “evidence base for pharmacogenetic testing should be informed by…the characteristics of the outliers.”

The lead investigator for the consortium, Stanford University’s Russ Altman, reported that his team plans to tweak the dosing algorithm through an ongoing study of 100 patients from the San Francisco Bay area and report the data on the PharmGKB website. Altman and the other authors also admitted in the report that research still needs to be done on whether the improved dosing leads to better clinical outcomes. This is where the NIH’s upcoming clinical trial falls right into place.

NIH will now embark on a prospective double-blind clinical trial where approximately 1,200 subjects will be split into two groups, one being prescribed warfarin according to clinical data and one using both clinical and genetic data. GenomeWeb Daily News reports that a European team at Newcastle University and the University of Liverpool are also working on a similar clinical trial that will take place at 13 research centers in seven countries where they expect to enroll 2,700 subjects.

The question of clinical outcomes is an important one since the true potential of pharmacogenomics for improving our nation’s health lies not just in the scientific advancements but in the clinical effectiveness advancements it generates. Indeed, pharmacogemomics-based treatments, like all treatments, need to pass the practicality test if biomedical innovation is to make a constructive contribution to a larger system-based healthcare infrastructure.

Last month, for instance, ScienceDaily reported on an analysis conducted by the University of Cincinnati which found that even though pharmacogenetic-based dosing of warfarin improved outcomes, it did so at very high cost—$170,000 per quality-adjusted life year gained. The current rule governing the interpretation of most cost-effective analyses is $50,000 per quality-adjusted life year gained.

The main focus of the UC research was to determine whether pharmacogenetic-dosing decreased the risk of major bleeds. The analysis was conducted on the combined data of the only three clinical studies of pharmacogenetic-guided warfarin dosing that had been conducted by that time. The researchers also found that there is only a 10 percent chance that the pharmacogenetic-based would be cost effective. The lead investigator, Dr. Mark Eckman, recommended a number of conditions that could make the dosing more cost-effective.

Specifically, it should be used for patients who have a high risk for hemorrhage, prevent more than 32 percent of major bleeding events, be available within 24 hours, and cost less than $200.

He recommended that the upcoming NIH clinical trial “examine the impact of pharmacogenetic-guided dosing on bleeding risk and monitor outcomes long enough to determine the true duration of benefit,” suggesting that patients with a higher risk of bleeding should not be excluded if it is determined that they need warfarin. Eckman summed it all up by saying, “personalized, predictive medicine offers great promise, but we need to carefully examine the benefits and understand the cost-effectiveness of such strategies before we spend a lot of money on very expensive tests.”

Image: AP/ED ANDRIESKI

While she wrote about the likely withdrawal of the rule, she also pointed out that its original implementation relied on some dangerous concepts. Some things conservative officials neglected when implementing the rule:

1) Requiring a health care provider to do his or her job is not discrimination.
2) Providing a referral for a service is not morally equivalent to providing that service yourself.
3) A refusal to provide care can harm patients.

More from Arons here.

The stimulus package President Obama will sign into law today contains $1.1 billion for comparative effectiveness research. The money will support work to determine what treatments are effective for various conditions and which are boondoggles that unnecessarily increase healthcare costs.

Over at Gooznews.com, Merrill Goozner calls the provision “half a loaf,” lauding its inclusion, but expressing dismay at the fact that the conference report reads: “The conferees do not intend for the comparative effectiveness research funding included in the conference agreement to be used to mandate coverage, reimbursement, or other policies for any public or private payer.”

Donald Light explained the benefits of comparative effectiveness in his Science Progress article, “How Reducing Negligible Risks Drives Up Health Costs.” In it, he took a close look at the clinical trials for Crestor, a statin, and the subsequent media frenzy that followed the publication of results that it “slashed nearly in half” the risk of cardiovascular trauma for people taking it. In this case, “slashed in half” meant reducing risk from 1.36 percent to 0.77 percent, while offsetting the cardiovascular benefits with an increased risk of diabetes. Light goes on to explain that the current FDA new drug approval process more or less requires that new drugs “just have to be better than nothing.”

Several weeks ago, fifteen of my primary care-internist colleagues and I sat in a midtown skyscraper in a classroom fitted with a laptop computer for each of us. Coffee cups in hand, we embarked upon a two-hour class—the first installment of a ten-hour course—to learn to use a multispecialty electronic medical record (EMR).

The EMR our medical center has decided to launch is elegant, with lots of pop-ups, color-coding, and an amazing ability to collect and generate data. Our instructors pointed out that the new system was more than just a computer to write notes or order prescriptions. Our practice has had that capability for years.

The beautifully scribed notes of the past, sequestered in a doctor’s office or lost in transition in Medical Records, did little to disseminate knowledge or share the insights essential for patient care.

No, this new system was different. It was a medical information superhighway. It connected you with colleagues throughout the medical center by means of a shared medical record. Between sips of coffee, we were told of the new system’s capabilities: If you want to know about your patient’s last visit to the urologist or send a pre-op clearance note to his cardiac surgeon, your colleague is but a click away. Order a drug that is incompatible with the patient’s medication list, and the EMR will warn you away from your choice and steer you clear of a pharmacologic mismatch. Beyond its capability to promote safety, it also can facilitate outcomes research.

Although I was none too thrilled to trudge downtown for training, I must admit that typing up a mock patient visit on the computer was fun. Since it is not altogether different from ordering a book on Amazon or searching UpToDate for medical information, it was not entirely unfamiliar, but it was still novel for a middle-aged doc whose career in medicine began before computers, much less the advent of information systems.

You see, I am part of that cusp boomer generation that came of age before the Internet. Although I am now wedded to a PDA at all hours of the day, night, and weekends, my worldview was shaped in an analog time right before the digital onslaught—now an almost premodern experience.

In high school, my chemistry class was the last to use the slide rule. We thought they were cool and a marker of scientific sophistication, at least until the first hand-held calculators displaced them. By our senior year, physics was made simpler by my little Casio computer, but I’ll always be glad to have experienced the seventeenth-century charm of a slide rule. It might have been centuries old, but it taught you to appreciate logarithms in a way the Casio did not.

In medical school, my class was the last to do pathology solely with glass slides and microscopes. The following year, an innovative pathology professor started to use primitive Apple computers to display some images. No longer were students wedded to one hundred prized slides that they lugged around in old wooden cases. The possibilities were limitless.

Because I am of a certain age, the age of informatics has been trailing me and will chase my generation forever. This is especially true when it comes to the galloping arrival of the EMR. When we were residents in the late 1980s, we would pride ourselves on how our charts read and looked. The chart was a place to tell a patient’s story from our point of view. Although we had all been trained in the architecture of the medical note and the progression from Chief Complaint (CC) to History of Present Illness (HPI) on down to Assessment and Plan (A/P), each of us did it a bit differently. Each of us had our own voice. I recall marveling at the charting styles of my colleagues and professors: the long, obsessively complete note of the intern versus the almost aphoristic musings of the attending—the former chock full of unorganized information, and the latter synthetic in its encapsulation of the problem and plan of action. And in that transition, through our writings in the medical record, we all learned how to think as doctors.

The notes were also often handsome. Although the rule was that all were to be written in black ink, some engaged in a degree of civil disobedience by expressing themselves in another color (myself included). I recall a pioneering female doctor-professor who used a fountain pen and wrote in a turquoise hue. Each of these notes was reflective of a grand personality and as recognizable as the author’s signature.

As a resident, I used to “specialize” in notes depicting occurrences of angina. In the premodern age of fancy twelve-lead cardiograms that would print out the whole thing out on a single sheet, we would run long strips one lead at a time. Later we would collect the strips and label them carefully. As an intern I learned from a resident how to cut the strips into usable samples using a credit card as a template for gauging the width. Once placed in the chart, these notes were a thing of beauty and a testament to our earnest efforts.

But as beautiful as my EKGs were, they were of limited utility. In retrospect, they are now reminiscent of the quaint temperature charts of the late nineteenth century, so carefully drawn by our predecessors. Because they were unofficial EKGs, unread by cardiology, they did not always make their way into the permanent medical record. If they did creep through, they—along with the entire chart—were often “lost to follow-up” in Medical Records until the chart had been “broken down” for billing purposes. That would work out fine if the patient spaced his admissions for angina to the hospital to once every three or four weeks, but not if there was a rapid readmission. In that case, the chart was often unavailable, with no one having access to a current cardiogram or list of meds.

It is for these reasons that my rational self applauds the new electronic medical record. The beautifully scribed notes of the past, sequestered in a doctor’s office or lost in transition in Medical Records, did little to disseminate knowledge or share the insights essential for patient care. With the EMR, data is always available in the service of patients. Our ability to communicate findings has no hiatus.

But still, my romantic self worried that something has been lost with the homogenization of the medical record. Our instructors told us that we could write whatever we wanted in a particular box as “free text.” In the past, we were free to write and construct the medical narrative as we saw fit. Today, it seems we need to be liberated from a grid that has the potential to depersonalize the medical record by squelching creativity and silencing helpful narratives.

The creation of this virtual yet patient-specific social network will force us to create a new balance between privacy and information exchange, both as individual physicians and as members of practice communities.

While the medical record could never be equated with the doctor-patient encounter itself, it was the narrative reflection of that dyad by one of its participants. As we think about pop-ups and automated prompts, will our engagement with patients become similarly muted of affect? Will it deprive us of an empathic response? This concern is more than the well-rehearsed literature, dating back to the 1990s, about having a computer in the exam room. It is about the sentience of an information system, a sentience with which physicians might engage at the expense of engagement with patients. Will the EMR turn the doctor-patient relationship into a new sort of triad, with the EMR itself now acting as proxy for all who care for the patient? If the EMR is the vector of information out to colleagues and the recipient of data from medical cyberspace, what does that mean for the privacy, indeed the intimacy, of our relationship with patients?

In our class, we learned that we would have the option of making some notes “sensitive” and off-limits to other readers unless they are specifically authorized. We heard that the psychiatrists and obstetrician-gynecologists are availing themselves of this option. If it now takes a medical village—and a shared medical record to provide care—are we therefore also responsible for each other’s work? And if so, are we obliged to collectively share information, sensitive or not, with each other?

My psychiatrist and obstetrician-gynecologist colleagues’ urge to demarcate special sections of the EMR speaks to some of these issues. But it also betrays a deeper concern about how the EMR might transform the doctor-patient relationship. Its ability to morph the medical record from a practice-based document into a communal one will move patient care into a social network, beyond any exam room and outside the scope of any single provider or solitary doctor-patient relationship. The creation of this virtual yet patient-specific social network will force us to create a new balance between privacy and information exchange, both as individual physicians and as members of practice communities.

My first morning in clinic with the new system put some of these speculative concerns about the EMR to the test. As a primary care doc, one of my biggest challenges is coordinating patient care and keeping abreast of all the other doctors my patients may be seeing. The EMR solved this problem. With a simple click on “chart review” I could see which physicians my patients had consulted and get accurate, up-to-date information. This was far better than relying solely on incomplete or poorly recalled patient histories about what happened between visits or being at the mercy of specialty consultants who sometimes send a note outlining their findings. Now I had access to their medical records and their thoughts in real time.

I felt empowered by this wealth of information and my newfound ability to share recommendations with colleagues. This became immediately clear when I “signed” a note for a patient needing pre-op clearance for a gynecological procedure. My electronic signature turned the medical record into a virtual e-mail. The gynecologist had immediate access to my suggestions and a way to get back to me.

But it was more than medical e-mail. I also had the sense that a window on my practice was now opened. I am now writing for a wider audience than before. My charts are now public documents in the context of the local medical community where one’s local reputation as a clinician is forged. All care is now witnessed, open to local peer review: others can read what I write and assess its content, clinical judgment, and quality.

The EMR will never compare with the aesthetics of the old paper chart, but it has a functional capacity that the conventional medical record will never have. Like the paperback, which supplanted the medieval illuminated manuscript, the EMR has a mass appeal; within medical communities, it will distribute information beyond a sequestered few to those who actually need to be informed.

I still lament the passing of the beautifully scribed medical record—and remain concerned about confidentiality and the doctor-patient relationship—but I also welcome what information technology can do to minimize discontinuities of care and the medical errors that stem from miscommunication. Most of all, I welcome what the EMR has done to reestablish relationships with colleagues. As dispersed as we are in our separate clinics across the medical center, we are actually talking to each other and sharing our charts. This web of care is already appreciated as an operational improvement over the status quo. I suspect it will also become a way to collectively reaffirm and redefine our values as a healing community. Linked through technology, we can now articulate what constitutes scientifically sound and humanistically informed medical practice in the information age.

Joseph J. Fins, M.D., F.A.C.P. is Chief of the Division of Medical Ethics at Weill Medical College of Cornell University where he serves as Professor of Medicine, Professor of Public Health and Professor of Medicine in Psychiatry.

© The Hastings Center. Reprinted by permission. This article originally appeared in the Hastings Center Report, vol. 38, no. 5 (2008), available at: http://www.thehastingscenter.org/Publications/HCR/Detail.aspx?id=2216&page=1

Now hospitals must evolve again so that their moral identity is based on more than a commitment to scientific rigor and technical proficiency. Science and technology are necessary, of course, but not sufficient. Hospitals also must attend to markers of excellent patient care in a broader sense, using a wider-lens approach that focuses on change within organizational systems complexity.^[2]

Now, it is time to move beyond the provision of merely technically feasible medical intervention. It is time to create mechanisms to forestall the use of alluring technology for its own sake, when it will not provide meaningful functional benefit. It is time to shift from the ineffective cost-cutting strategies that have reduced the practice of hospital medicine to running procedures as quickly as possible, so as to stabilize a patient for rapid discharge.

These outdated health care delivery approaches have resulted in hospital practice that is harmful to patients, families, and clinicians. For patients it often results in overtreatment. For families it results in feelings of dissatisfaction with hospital staff. For clinicians, it is crushing to morale and results in burn out. “Health-care costs are being treated as if they were largely an economic problem, but they are not,” observed the noted economist Lester Thurow. “To be solved, they will have to be treated as an ethical problem.”^[3]

In short, it is time to reimagine hospital care.

Hospitals must reorganize their systems of care delivery if they expect to successfully meet the moral ends of medicine—that is, to treat pain and suffering, cure if possible, and honestly acknowledge when the patient’s disease cannot be cured. We need to find ways to enable hospitals to address systems complexity directly as they work to refocus care on what patients need to improve their health and functional status—or in the case of dying patients, what they need to die well. By doing so, morally grounded cost savings can accrue and hospital care in the United States can return to a leadership position in global health.^[4]

These will not be easy tasks. Hospital care is complicated, expensive, and often emotionally charged. And, with our population aging, we will see sharp increases in the number of patients with chronic conditions who can be expected to be in and out of the acute care setting over the course of their disease. In the United States, the hospital is often the last place for medical care—20 percent of all U.S. deaths now occur in an intensive care unit or immediately thereafter.^[5] At the same time, satisfaction with hospital care continues to be low.^[6]

Numerous variables—including the continual introduction of new technologies, the burdens patients and families experience when they are expected to control medical decision-making, rampant fears of liability, dying as a chronic disease, and radical changes in physician training and health care cost coverage structures—all converge in the hospital setting to create systems of daunting complexity. One response to this complexity is to seek to overcome it through personal effort. Hard-working clinicians, administrators, and hospital support personnel focus on their own domains of work, trying to improve the outcome of their assigned tasks and thus take better care of patients.

Yet the generally accepted goals of quality improvement in health care—that care should be safe, effective, patient-centered, timely, efficient, and equitable—cannot be achieved without engaging system complexity in hospitals. As was made clear in “Crossing the Quality Chasm,” a landmark 2001 report from the Institute of Medicine, “Trying harder will not work. Changing systems of care will.”^[7]

In the pages that follow, we will present two case studies that illustrate some of the systems complexities of modern hospital care. We follow these cases with solutions that require changes at all levels of systems complexity, working to paint a picture of wheels and gears within wheels and gears.

Case One: Ms. K’s Repetitive Admissions

Ms. K, 56 years old and living with her 59-year-old sister, is brought by ambulance to the emergency department in a diabetic coma. Ms. K is transferred to the intensive care unit where, during the next 24 to 36 hours, she is stabilized. Although she is still weak, at this point she is medically stable enough to be transferred out of the Intensive Care Unit and onto a general medicine service. The ICU is in need of beds, with critically unstable patients stacking up in the emergency department.

Ms. K’s transfer orders call for her to receive diabetic education before she is discharged from the hospital. By the time Ms. K is transferred out of the ICU, however, it is late in the evening. The next day, the floor nurse calls the diabetic nurse educator, who comes and thoroughly explains the necessary medications and the importance of adhering to the prescribed dietary regimen. Thereafter, Ms. K is discharged home. About three months later, Ms. K comes back into the ICU, once again through the emergency department, for the same problem.

During rounds in the ICU, the first-year resident physician presenting the case summarizes the physiological evidence showing no co-morbidities, that is, no other serious medical problems. The first-year resident also points out that the patient has not been recently ill, nor is she a drug addict or alcoholic—all possible explanations for the patient’s present problem. Therefore, when the first-year resident ties up the patient’s symptom profile, clinical examination findings, laboratory and other diagnostic test results—concluding that the patient’s present problem is from medication non-compliance for her diabetes—the resident’s assessment goes unchallenged by the rest of the clinical team.

By happenstance the third-year resident physician who took care of Ms. K on the floor three months earlier is now rotating through the ICU. She remembers the patient from the floor, and her medical ethics training has made her alert to the issue that merely technically competent care of the patient, at the time the patient is in front of the treating clinician, often is not sufficient for excellence in the art of medicine. Thus, the conclusion of the first-year resident leaves the third-year resident uneasy because “intentional non-compliance” (the term “non-compliance” casts the patient in a pejorative light) somehow does not jibe with the resident’s recollection of Ms. K.

The third-year resident manages to steal time to read through archived chart entries and discovers that the patient had been admitted six times in the past three years to various area hospitals in a diabetic coma. Previous chart notes confirm that the sister with whom Ms. K lived was caring and attentive, although the resident had formed an impression of the sister as not really fully appreciating what medication Ms. K would need to take when she returned home.

The resident, after continuing to read through pages of archived charts, finds mention of below-normal intelligence in the patient, which suggests that when the medication and dietary regimens had been explained, the patient might have been unable to retain the information. This likely gap in the patient’s understanding, coupled with the probability that Ms. K’s sister did not fully grasp the gravity of adhering to tight dosing requirements, could account for the recurring problem.

With this information, the third-year resident realizes that both the patient and her surrogate need additional assistance. By the time the third-year resident figures all this out, however, and realizes that social work needs to be called to arrange for a visiting nurse or nurse’s aide to come into the patient’s home frequently enough to check on medication management, the patient is ready for discharge. Realistically, it will probably take the social worker a day or two to get the needed home health care supports set up.

Applying a Systems Complexity Approach to Ms. K’s Care

That Ms. K returns again and again to her local hospitals for the same problem reflects bad patient care. It is dangerous for Ms. K to repeatedly experience a diabetic coma. Viewed at the broadest level, it is expensive for the national health care system. From the perspective of those rendering the care, it is dispiriting, given that diabetic coma is, under normal conditions, an avoidable event.

Because of systems complexity, however, the repetitiveness is even difficult to spot. At one level, her care was flawless. The ICU team (that is, residents, attending physician, nurses, unit clerks) took medically appropriate actions while the patient was in the ICU; transfer orders to the floor were written properly and followed; and discharge planning and education were carried out. Nor is this a case of a patient facing socioeconomic barriers. Ms. K has insurance, so payment for care and pharmaceuticals is not the problem. She lives with her sister, with whom she has a loving relationship, so this is not a matter of having an isolated patient without adequate social support.

Rather, implementing solutions that will work for patients like Ms. K, not merely tinkering with old ones that did not, will require reinventing how we think about hospital operations. Given that information crucial to proper care can easily become invisible in a complex system, hospitals need to invest in the time, space, and staffing that would allow problems like Ms. K’s to be spotted early enough for effective intervention. This investment in problem case identification is needed for outpatients and inpatients alike, because coordinated outpatient care, or the lack of it, directly affects hospitals.

Although time, physical space and professional staff cost money, they are integral to all systems and subsystems influencing and embedded within health care delivery. Taking the short-sighted approach of looking for yet more ways to cut costs is precisely the worst strategy for managing costs, systems complexity and ethically justifiable medical care.

For Ms. K, smart systems complexity management could start with reinvention of hospital staffing patterns. Smart systems reinvention would include attaching a clinical social worker to Ms. K at her second admission. This did not happen in the case because hospitals have generally reduced the role of social workers to discharge facilitators. To achieve ethical and effective care of Ms. K, her social worker would serve as the social issues coordinator.

This reimagined social worker is the fulcrum for smartly coordinated care, linking all relevant medical, ethical, and social information so that it is not lost in a system of ever-changing medical teams. Ms. K’s social worker would assist in the coordination of all meetings about patient needs, decision-making, and transfers to various floors and units. To reduce the post-discharge risk of another bout of diabetic coma caused by non-adherence, Ms. K’s social worker would be expected to coordinate with Ms. K, her inpatient and outpatient clinicians, home health support personnel, and her sister, tracking Ms. K’s post-hospitalization progress long enough to avoid, if at all possible, rehospitalization.

What is being called for here is not simply more social workers doing real, clinical social work. Rather, the addition of more clinical social workers is one instance of the broader and more fundamental change that comes with recognizing, and responding to, the systems complexity of health care. For example, the preventive care coordination for which an augmented clinical social work staff would be responsible implies other changes, not the least of which is that information be accessible through widely adopted and compatible electronic systems of health records.

Case Two: To Transfer or Not To Transfer Mr. J.

Mr. J., an active 72 year old, lives in a rural area with his wife. On a cold day in January, Mr. J has a massive brain bleed and a cardiac arrest. His wife calls 911, and the local emergency personnel arrive within a couple of minutes, immediately beginning cardio-pulmonary resuscitation. On their way to the nearest community hospital, they regain Mr. J.’s pulse, which is sustained in the hospital’s emergency room.

Within minutes, Mr. J. is transferred to the hospital’s ICU. The ICU’s attending physician immediately recognizes that Mr. J’s brain bleed is still evolving. The attending physician has the hospital’s on-call neurologist contacted; they confer and agree that the patient may be a surgical candidate. The surgery, however, cannot be performed at the community hospital, as there are no local neurosurgeons. The ICU attending physician has the closest regional hospital contacted that can accommodate a patient in Mr. J’s condition. The accepting neurosurgeon at the regional hospital communicates with the rural neurologist, obtaining as much information as possible while the patient is being airlifted by medical helicopter to the accepting regional hospital.

Mr. J arrives at the distant, regional hospital, where the accepting neurosurgical staff immediately evaluates him. The team determines that Mr. J is not, after all, a surgical candidate. The patient is transferred to the medical ICU, where he languishes for weeks and eventually dies, after a rancorous series of encounters between the medical team and the family about establishing and sustaining realistic expectations for meaningful functional recovery in the patient. Clinically, the patient arrived unconscious and never improved during the many weeks of his ICU stay.

Applying a Systems Complexity Approach to Mr. J’s Care

As in the first case, on the face of it Mr. J’s care was technically adept. The emergency medical team ran a successful resuscitation in the field. At the rural hospital, Mr. J was evaluated quickly and competently by the appropriate complement of nurses, emergency room physician, ICU attending physician, and on-call neurologist. The determination that the patient might be a surgical candidate was made expeditiously, as was the coordination with the closest hospital that could perform the surgery and the airlift to get the patient to that next hospital. Unfortunately, all of that activity only ended up with a patient who was not, after all, a surgical candidate, in a hospital far from the patient’s home, and with family who had to traverse long distances while experiencing a roller coaster of emotions and eventually dashed expectations.

If, however, we take proper account of systems complexity throughout our hospital systems and subsystems smartly, we can reduce the misery of these situations. We can provide families and friends the environment and resources they need to process calamitous medical events and, where such turns out to be the need, to begin grieving. One of the solutions is to reinvent our hospital spaces to more currently match the severity, acuity, and social complexities 21^st century patients present.^[8]

Many hospitals have emergency rooms. Many have ICUs. But most have nothing in between other than standard lower-level acuity care units. So in Mr. J’s case, once the regional hospital’s neurosurgical team had decided that, for whatever panoply of conditions specific to Mr. J’s clinical status, he was not a surgical candidate, the only safe place in the hospital for Mr. J was the medical ICU. He was on a ventilator (a breathing machine), and there are few places in a hospital other than an ICU that have the staffing capability to manage patients on ventilators.

Even if, over the days and weeks of Mr. J’s ICU stay, he had been weaned off the ventilator and able to breathe on his own, his blood pressure was unstable, which meant that he still needed medications to artificially elevate his blood pressure. His immune system was also impaired, and he continued to need antibiotics. Unable to swallow, he needed these medications administered through intravenous drips, none of which can usually be managed anywhere in the hospital other than the ICU.

If, however, high acuity hospitals—the kind where patients like Mr. J are taken—were to create intensive care step-down units, then it is possible that even such hi-tech care as is required for critically ill, stable patients could be provided more humanely and with less expense. While the systems change solutions suggested for our first case study almost completely revolved around altered staffing patterns, here the focus is on altered staffing patterns and redesign of physical space.

An intensive care step-down unit, a unit some might call a hospice ICU or by some other comparable title, would be quieter. For many of its patients, the goal would be reducing aggressive, non-beneficial care. The primary oversight would be through the nurses, with expensive physicians on call as needed rather than as primary staffing for the unit. Wake/sleep lighting would be normalized. Family and friends would be welcome at any time. Such a unit would build time and space back into the dying process.

An even more fundamental reinvention solution would prevent Mr. J from ever having had to be moved in the first place. What’s more, the technology already exists.

The reason Mr. J had to be airlifted into the higher acuity hospital was because neurosurgeons make “go/no go” surgical decisions, and most community rural hospitals do not have neurosurgeons available. The neurologist at Mr. J’s rural hospital, however, would be expected to be able to conduct, under the guidance and supervision of a neurosurgeon, an examination sufficient to allow a watching neurosurgeon make the surgery decision. That is, if Mr. J’s rural hospital were equipped with the requisite telemedicine technology, the regional hospital’s neurosurgeon could direct and “watch” the examination needed to determine whether or not Mr. J should be transferred.

It also is possible, given Mr. J’s particular clinical problem—a brain bleed—that although he might have been judged not to be a surgical candidate at first examination, he might have become one over the next several days. With the electronic technology to do the original examination remotely, the geographically distant neurosurgeon could continue to “watch” Mr. J and, if the evolving clinical situation justified doing so, make a different decision.

Applying a Systems Complexity Approach

A paradigm shift towards thinking about hospital processes from the perspective of systems complexity and systems change will be difficult to accomplish.^[9] But this new approach to excellence in hospital care is necessary. Achieving this shift will take the combined efforts of many disciplines working together and well-conceived policy incentives. It will also take a willingness to reimagine physician-patient relationships in new ways.

Relevant here is the reality that hospital medicine is delivered by teams. Hospital clinicians appreciate this, even if others do not. Although the traditional model of the doctor/patient relationship is still central to physicians’ professional identity, appreciation of fiduciary responsibilities and developing the character of the virtuous physician, the model is no longer the lived experience of most physicians or patients. For the hospital patient, the traditional model has been replaced by a dizzying array of doctor/patient encounters. Especially in teaching hospitals, patients and families interact with so many doctors, in such staccato exchanges, that it is virtually impossible for the traditional concept of the doctor/patient relationship to remain meaningful. This reality of contemporary hospital medicine has important implications for health care delivery organization.

In Ms. K’s case, her doctors all provided technically competent and, we will assume, empathetic care. But each time Ms. K came into the hospital, a different attending physician was on-call. The residents responsible for her care in the ICU on previous admissions had long shifted their unit rotations, and the one or two residents who might have crossed Ms. K’s path, as well as her nurses, were on different shifts during her brief stays. The fact that Ms K had health insurance does not imply that she had a primary care physician who would be noted in a hospital chart. That the third-year resident remembered Ms. K from the floor and made the time to go back through old charts was lucky indeed.

Given the relatively simple medical problem Ms K presented, the speed of her transfers from emergency department to the ICU to the floor and then her discharge, the system of care did not encourage the clinicians to discover the high number of previous admissions or the underlying causes that would account for her in-and-out hospitalization pattern. The time pressure on physicians that force them to focus almost exclusively on the scientific and technical aspects of care; the lack of other clinical professionals, such as clinical social workers who could devote time with the patient and her sister to gain a broader perspective on care issues; the inability to easily access previous hospital admission information—all of these factors conspired so that Mr. K’s technically flawless care was actually poor.

For Mr. J, ill fortune dictated his death, and rescue medicine was not available to save him. What could have been averted were weeks of nonbeneficial care and much family and clinician distress, had hospital space been organized to provide critically ill, dying patients and their families care that meets their special medical and moral needs in units other than standard ICUs. Indeed, if already existing technology were disseminated properly, critically ill, dying patients like Mr. J. can remain well cared for in rural hospitals.

We need to take a fresh look at hospital staffing. Hospital staffing patterns must be reoriented to provide patients with the caring attention they have always needed and will always need within a health care system that will only become more technologically complex. Determining exactly how to achieve this goal is a problem fraught with complexity. Hospital clinical care is, today, so heavily technological that to expect physicians, especially physicians still in training, to be as skilled at the nontechnical parts of the job as at the technical parts may be unrealistic.

The solution is not to simply try to reduce the technological knowledge required of clinicians. In time, the requirements for physicians and nurses to understand more and more technologically advanced, scientifically justified procedures will likely become more, not less, integral to hospital medicine. Instead of adding to physician and nurse burdens, we have to become more skilled at managing continuous flux and change within complex systems, becoming creative about arranging who does what in the care of hospital patients.

Another one of these system-wide, systems-redesign solutions is in the communications domain. One piece of smart complexity management here is for hospital professionals, other than physicians, to take over some of the tasks previously thought of as being only under the purview of a physician, such as discussions about end-of-life care planning, freeing up physicians to do the technical parts of medical care that only physicians are trained and licensed to do. Instituting such a change, however, requires overcoming entrenched patterns and attitudes. Many physicians believe that talking to patients about medical care planning is solely a physician prerogative, even though physicians may never have been adequately trained in effective communications skills and, especially as the prospect of successful rescue medicine grows bleaker, often shy away from exercising their assumed authority.

The result is that important planning conversations never occur. This problem is magnified by the related systems problem of the misguided cost-cutting strategies that have decimated hospital’s clinical social work staff and continue to act as barriers to building clinical ethics, palliative care, and hospice programs into daily hospital operations. The challenge of rethinking traditional hierarchy and professional obligations long embedded in the practice of medicine is difficult indeed. But these traditional practices, along with all other hospital practices and systems, must be open to review and they must be changed wherever necessary.

Reform of health care must include steps to encourage a paradigm shift from hospital medicine that is focused too narrowly on procedural skill to the realities of 21st century medicine, which is characterized by complex systems surrounding diagnostics and procedures and is delivered by teams of clinicians and support personnel. This is a task that we must undertake and complete successfully for the sake of everyone who may someday be a patient in a hospital—that is, all of us.

About the Authors

Evan G. DeRenzo, Ph.D., is Senior Bioethicist, Center for Ethics, Washington Hospital Center, Washington, D.C. Adjunct faculty at the Johns Hopkins University, Graduate Program in Biotechnology, she received her Ph.D. from the University of Maryland in Human Development with a concentration in gerontology. She serves or has served as consulting bioethicist to a wide variety of private organizations and Federal and Maryland state agencies, on multiple Institutional Review Boards and Data Safety Monitoring Boards, and on numerous hospital and professional association ethics committees, including the global ethics committee of the Association for Clinical Research Professionals and the World Federation of Societies for Biological Psychiatry. She has published widely in the areas of clinical ethics and human participant research ethics, and is the Editor-in-Chief of the Journal of Hospital Ethics.

Jack Schwartz is Visiting Professor of Law and Senior Health Law and Policy Fellow at the University of Maryland School of Law. He formerly served as an Assistant Attorney General and Director of Health Policy in the Maryland Attorney General’s Office. His undergraduate work was at the University of Maryland Baltimore County, and he then went to Yale Law School. Prior to joining the Maryland Attorney General’s Office in 1982, he held a series of senior staff positions at the Federal Trade Commission in Washington. Currently, he is a member of an institutional review board at the National Cancer Institute, a data and safety monitoring board at the National Institute on Aging, the Bioethics Committee of the Washington Hospital Center, a State of Maryland advisory committee on infections in health care facilities, and the advisory board of the Maryland Healthcare Ethics Committee Network. In recent years, he served as a member of the American Bar Association’s Commission on Law and Aging, a senior consultant to the National Bioethics Advisory Commission, a member of a national advisory committee for the Robert Wood Johnson Foundation, the State Advisory Council on Quality Care at the End of Life, the Maryland Stem Cell Research Commission, and the Maryland Task Force to Study Electronic Health Records. He writes and lectures frequently on legal, policy, and ethical issues in health care.

Stephen R. Selinger, M.D., FCCP, is President of Pulmonary & Critical Care Associates of Baltimore, currently the largest pulmonary and critical care group in the United States; staffing six hospitals and nine critical care units, and Director of Critical Care Services at Franklin Square Hospital. Dr. Selinger, a graduate from Johns Hopkins University School of Medicine 1979 and Assistant Professor of Medicine Johns Hopkins Hospital from 2003-2004, is currently Clinical Assistant Professor of Medicine, Education Office University of Maryland School of Medicine 2003-present. He is also Associate Chairman, Department of Internal Medicine, Franklin Square Hospital Center, and the recipient of multiple Excellence in Teaching awards from Good Samaritan Hospital; and Distinguished Attending of Year awards from Franklin Square Hospital. Dr Selinger is a member on multiple hospital committees and MedStar TICU that creates and implements protocols and tools to improve quality of care in critical care settings.

Disclaimer: This report contains the views of the authors, only, and does not represent the policies or procedures of any institution or organization to which any of the authors are affiliated.

Note: Portions of this article will appear in E.G. DeRenzo, “Seeking Excellence in Hospital Care: Evolving toward a Systems Approach,” in The Journal of Clinical Ethics 20, no. 1 (Spring 2009): in press.

Notes

[1] P. Starr, The Social Transformation of American Medicine (New York: Basic Books, 1982), 145.

[2] R.D. Stacey, Strategic Management and Organizational Dynamics: The Challenge of Complexity (Harlow, UK: Prentice Hall, 2003).

[3] Thurow LC., “Learning to say no,” NEJM. 311(24)(1984):1569-72, p. 1572

[4] S. Brownlee and E. Emanuel, “5 Myths on Our Sick Health Care System,” The Washington Post, November 23, 2008.

[5] R.D. Truog et al., “Recommendations for end-of-life care in the intensive care unit: A consensus statement by the American Academy of Critical Care Medicine,” Critical Care Medicine 36 (3) (2008): 953-63.

[6] S.M. Dy, H.R. Rubin, and H.P. Lehmann. 2005. Why do patients and families request transfer to tertiary care?: a qualitative study.” Soc. Sci. Med. (61):1846-1856.

[7] Institute of Medicine, Crossing the Quality Chasm: A New Health System for the 21st Century (Washington, D.C.: National Academy Press, 2001).

[8] See Mokwunye NO., “A case study of cost, mortality, and quality of life outcomes of inappropriate and appropriate admissions to a medical intensive care unit” Dissertation Abstract International, 69 (4A) (2008); Smith TJ, Coyne P, Penberthy L, Hager A, Hopson MA, “A high-volume specialist palliative care unit and team may reduce in-hospital end-of-life care costs,” Journal of Pallliative Medicine, 2003: 699-705; Cohen SR, “Changes in quality of life following admission to palliative care units,” Palliative Medicine, 2001: 363-371; Goldney R, Bowes J, Spence N, Czechowicz A, Hurley R, “The psychiatric intensive care unit,” Br. J. Psychiatry 1985: 146:5054; and Winkler D, Scharfetter J, Kasper S, Frey R. “Ethical Issues and Intensive Care in Psychiatry” Journal of Hospital Ethics, in press.

[9] T.S. Kuhn, The Structure of Scientific Revolutions (Chicago: University of Chicago Press, 1962).

Friday, Nature published an interview with former NIH Director Elias Zerhouni in which he talks about balancing the playing field between young and established investigators and providing for research in the midst of an economic downturn (HT: David Bruggeman at Prometheus):

What solution do you see to the NIH financial crisis?

The solution is that the economic situation has to turn around. I studied the NIH budget over time. And it’s directly correlated with the federal surplus and gross domestic product growth.

But look at the situation today. The economic stimulus package is $500 billion, with $1 billion for science. It’s outrageous. This is the future of our country. So now we’re subsidizing the industries of the past at the expense of investments in the industries of the future. It’s almost an insult, frankly.

The Washington Post followed up Saturday with a profile on Zerhouni that examined, among other things, the possibilities for redoubling the agency’s budget when President-elect Barack Obama takes office. Donald Light explored one point upon which that argument might turn last week–comparative effectiveness research as a way to reduce health costs. Wrote David Brown at the Post:

A major question facing the new administration is what role, if any, the NIH will play in the huge number of cost-effectiveness, comparative-effectiveness, quality-improvement and patient-safety studies that many health-care policy experts say must be done to get the full value of the products of medical research.

In an effort to make up for the impact of budget deficits on R&D spending, the American Association of Research Universities sent a letter to the incoming administration with six recommendations for how to help schools that support the economy in midst of the crisis using some of the $700 billion set aside for the financial services industry. The first proposal deals with ensuing access by helping students secure the grants and loans to, and the remaining five deal with improving academic infrastructure–both physical buildings and research grants. The Chronicle news blog has a summary, and Science Insider has the full letter, which is short.

Rick Weiss confronted the issue of NIH funding earlier this year and wondered if there wasn’t a spare $2 billion sitting around that Congress could invest in biomedical research for the health of the American public.

Bloomberg News announced, “AstraZeneca’s Crestor slashed the risk of heart attack, stroke and death by nearly half in people with normal or low cholesterol in a study, potentially opening a way to save the lives of thousands seemingly healthy people.” MSNBC News made the same announcement and then quoted the president of the American College of Cardiology: “This takes prevention to a whole new level.” Ron Winslow of The Wall Street Journal added, “The findings could substantially broaden the market for statins, the world’s best-selling class of medicines.” Except for USA Today, which worried about the high cost to patients, health plans, and the public, most announcements read like infomercials, excited about a major new market.

In short, this “pathbreaking” study that “takes prevention to a whole new level” actually offers little benefit and offsets it with a costly side effect.

These news headlines referred to a large clinical trial published on November 20^th in the New England Journal of Medicine that purported to demonstrate the effectiveness of Crestor—even on older patients with low cholesterol who scored high on a test for CRP, or C-reactive protein. CRP levels are used as an imprecise indicator of heart disease, though the molecule is “a nonspecific marker for low-grade inflammation,” according to Dr. Bernadine Healy, an adviser to U.S. News and World Report.

Almost no one learned that the “slashed nearly in half” reduction in cardiovascular trauma was tiny, from 1.36 percent to 0.77 percent, a difference of just 0.59 percent.

And almost none of the stories reported that the people taking Crestor had a comparable increased risk (0.60 percent) of getting diabetes. Those that did said the increase was “small,” but then so was the reduction in cardiovascular events. Suppose newscasters announced, “Major study finds patients taking Crestor for systemic inflammation experience less than 1 percent reduction in cardiovascular events and an equal increase in diabetes”? In short, this “pathbreaking” study that “takes prevention to a whole new level” actually offers little benefit and offsets it with a costly side effect.

American medicine is rife with such commercial bandwagon tests, procedures, and drugs. An effective policy solution would involve the creation of a comparative effectiveness institute that offered independent evaluations and subjected treatments to head-to-head trials in order to make recommendations about which ones are actually worth the money. President-elect Barack Obama’s health care platform calls for such an entity, and in August, Senate Finance Committee Chair Max Baucus (D-MT) and Senate Budget Committee Chair Kent Conrad (D-ND) introduced the “Comparative Effectiveness Research Act,” legislation that would create a nonprofit institute.

The closer you look, the less beneficial this breakthrough looks. For example, the investigators had screened out 80 percent of their sample so that the trial included only patients with a high CRP but without 13 other prevalent health risks. Those 13 risks include a history of cardiovascular disease, diabetes, arthritis, high blood pressure, cancer, hypothyroidism, or substance abuse. Also excluded were people taking hormone replacement therapy or lipid-lowering therapy.

Put another way, the vast majority of older women and men with low cholesterol and high CRP were excluded because they had conditions that might weaken the results. The trial aimed to select just those people who were most likely to produce a dramatic result but establish the basis for everyone to take the test to see if they have high CRP. If they do, they probably have other risks or behaviors like those people screened out of the trial, so taking Crestor (the most expensive statin) might or might not increase their risk for diabetes and reduce their risk for cardiovascular trauma.

Only a few news stories noted vaguely that Crestor itself has serious side effects. Reports to the FDA of kidney problems from patients taking Crestor exceeded reports for all other statins combined and led The Health Research Group in Washington, D.C. to recommend it be taken off the market. Crestor also lowers levels of CoQ10, a compound that helps generate energy and maintain muscle (including the heart muscle). Fatigue and weakness can result.

Moreover, the trial was stopped with 3.1 years remaining, and it is during this later period of testing when adverse side effects are most likely to surface. Running trials long enough to record benefits but too short to record adverse effects is a common practice in company-sponsored trials. It is one reason why adverse side effects are now epidemic, the 4^th leading cause of death, according to the Food and Drug Administration. As Professor Mark Hlatky at Stanford Medical School wrote in a cautious editorial, “Long-term safety is clearly important in considering committing low-risk subjects without clinical disease to 20 years or more of drug treatment.”

Currently, new drugs “just have to be better than nothing.”

The results of this market-driven trial were reported to the press in a way to get the public as well as the medical profession mobilized to generate large new revenues, thus making the media an agent of commercial interests. No mention was made of the fact that doctors are already prescribing statins to millions of patients to lower their cholesterol when in fact doing so does not reduce cardiovascular risk for those who have no other specific risk. The over-prescription of statins is costing everyone billions. Instead, the news emphasized how statins would now benefit millions more with low cholesterol.

The additional cost to the nation’s insurers, employers, and taxpayers of prescribing Crestor to patients with CRP is estimated to be $9.0-9.7 billion. The reduction of an already small risk would cost about $557,000 per life saved, according to James Stein at the University of Wisconsin School of Medicine and Public Health. That does not include the $80 for the patented CRP test that a much larger population would first have to take, nor the costs of treating new cases of diabetes and other side effects. Yet official guidelines for doctors appear likely to change and recommend the CRP test, whose patent is held by the principal investigator of the trial and his employer, Brigham and Women’s Hospital in Boston.

The main beneficiaries will be the patent-holders and AstraZeneca, the sponsor of the trial. Industry-sponsored trials are nearly 4 times more likely to produce results favorable to the sponsor’s product than independently funded trials, and this one is no exception.

In order to avert future misleading claims about new drugs and to help lower the costs of health care, the country needs an organization like the Comparative Effectiveness Research Institute proposed by Senators Baucus and Conrad. Their bill, S.3408, cosponsored with Senators Jeff Bingaman (D-NM) and Sheldon Whitehouse (D-RI), aims to control costs by improving the effectiveness of treatments used. It would have independent funding to assess the additional clinical benefit of new tests and interventions against their costs in order to get good value for our money.

Currently, new drugs “just have to be better than nothing,” according to Dr. David Barbe, chair of the American Medical Association Council on Medical Service. As Gail Shearer, the director of Consumer Reports’ Best Buy Drugs website and service said, “People are ready to talk about value.” The CRP-Crestor trial and bandwagon illustrates why an institute like this is a vital part of any health care reform under the new administration.

Donald W. Light is a professor of comparative health care at the University of Medicine & Dentistry of New Jersey and a senior fellow at the Center for Bioethics, University of Pennsylvania. His forthcoming book, The Risks of Prescription Drugs, will appear in bookstores this winter.

To help you understand this psychological phenomenon, I want you to imagine that you have ten years left in your career, and can choose between the following two income streams over those ten years: In the rising salary stream, you would start at salary X, and then receive a steady raise in your salary over the next ten years till you finish at salary X+Y. In the falling salary stream, you’d start right now at an salary of X+Y, and your salary would steadily decline across the ten years to end at salary X. Both choices would leave you with the exact same amount of salary over these ten years, only differing on whether your salary grows over time or declines.

What would you choose?

When I was given this hypothetical choice, I chose the increasing salary stream. I wanted to see my earnings get bigger over time, not watch them fall. Behavioral economist George Loewenstein created this hypothetical choice to illustrate an irrational side of human nature. You see, if I had been rational, I would have chosen the falling salary stream, because in theory I could have invested some of that early money and watched the interest compound over the ten years, leaving me richer at the end of the day than with the strategy I chose. Reason, in my case, lost out to instinct.

Most people, when given this hypothetical choice, are like me and choose the increasing salary. Most of us feel that our incomes are supposed to rise from year to year. The thought of watching our paychecks shrink over time goes against our instincts.

Recent battles over President Bush’s proposal to reign in Medicare costs revealed the power of this instinct. The Bush administration wanted to control costs in part by reducing physician reimbursement. On one level, the political battle was straightforward: A powerful interest group (physicians) stirred up fears to enrich itself. But on another level, the battle was more subtle. Physicians in this case weren’t after more money. They were trying not to lose money.

Daniel Kahneman won the Nobel Prize in part for elucidating people’s powerful psychological desires to avoid losses. (He conducted much of this work with Amos Tversky, who unfortunately died before the Nobel was awarded.) Kahneman and Tversky showed that people feel much worse about a modest loss than they feel good about a similarly-sized gain. In fact, people look more favorably upon a surgical intervention with a 90 percent survival rate than on one with a 10 percent mortality rate, even though there is no difference between the interventions. The mere framing of a choice as potentially involving a loss (of money, of life) triggers strong negative emotions. Human beings are hardwired with an aversion to losses.

Here’s the challenge raised by this psychological phenomenon: If we as a society want to control healthcare costs, one of the things we need to do is control physician income, which in the United States dwarfs that of most other advanced countries. (The most egregious physician incomes are generally earned by procedural specialists, with other groups, such as primary care pediatricians, receiving much more modest incomes.) But if we threaten to reduce physicians’ incomes, we will face tremendous resistance. Psychological resistance. Physicians won’t want to see their incomes go down.

The only way to control physicians’ income is to allow their income to grow over time, while controlling the rate of growth so that physicians’ incomes fall in relation to inflation. An oncologist making $400,000 last year (yes, that’s a pretty common income for such physicians) will probably fight aggressively to keep someone from reducing his income to $395,000 this year. Now, if through a new Medicare plan his income grows 1 percent this year, a rate significantly less than inflation, he will make $404,000. Psychologically speaking, he will feel like his income is growing, and he will probably be less likely to become politically active fighting the plan.

There’s another reason people fight hard to keep their incomes from declining: they often buy homes based on their income expectations. I’m not asking anyone to feel sorry for an orthopedic surgeon who, due to a loss of income, is forced to downsize from his 6,000 square foot home. But I am asking you to imagine yourself in that person’s shoes: you’ve bought your dream house and now, because of a shift in Medicare policy, you may have to move to a smaller house. How hard will you work to maintain your income? Will you donate money to a lobbying organization that will fight the Medicare plan? Will you buy a radiology practice, so you can start making money on your patients’ x-rays? Will you start operating on patients more often, including on elderly people who, in the past, you would have referred to a physical therapist?

Any politician who wants to change the healthcare system should heed the psychological power of loss aversion. Not to do so is a recipe for failure.

Peter Ubel, MD is the director of the Center for Behavioral and Decision Sciences in Medicine at the Ann Arbor VA Medical Center and the University of Michigan. His book Free Market Madness: Why Human Nature is at Odds with Economics—And Why it Matters (Harvard Business Press) is being published in January 2009.

Weiss’s Notebook

CAP Senior Fellow Rick Weiss covered science and medicine for The Washington Post for 15 years, and now he brings his investigative eye to science policy. From cloning and stem cells to agricultural biotechnology and nanotechnology, Weiss examines the issues at the intersection of cutting edge research and public policy.

“Personalized medicine” is the hot new buzz phrase in medicine. Why settle for diagnostic tests or therapies that were designed for the average patient, the thinking goes, when doctors can use new technology to pinpoint the specific details of your bodily biology and tailor tests and treatments to your exact medical situation?

The idea has potential and may gradually catch on as gene tests and other new technologies become more accurate and affordable. But a candid new report from the Department of Health and Human Services balances those lofty promises with a tally of the daunting challenges that scientists, doctors, patients, and insurers will face as the American healthcare behemoth tries to make the leap to the personalized medicine paradigm.

The issue is gaining importance because healthcare reform is high on the agendas of both Congress and the new president in the coming year. Proponents of personalized medicine want to make sure that whatever reforms are instituted do not undercut progress toward a more personalized future. At the same time, one can’t help but conclude, on the basis of the HHS report, that it is going to be an uphill battle to justify some of the upfront costs of the personalized medicine revolution, given the many technical, political, and educational hurdles that stand between where we are and where we want to get.

Some kind of reform is clearly needed. As HHS Secretary Michael O. Leavitt notes in his introduction to the 299-page report (a follow-up to one published a year ago), U.S. healthcare expenditures amounted to just 4 percent of the nation’s gross domestic product when he was born in 1951 but are now 16 percent of GDP and are projected to hit 20 percent by 2016—a trend he calls “not sustainable.” All told, today’s health expenditures of about $2 trillion are expected to double within less than a decade.

The core of the problem, as described in the report, is that Medicare—by far the nation’s largest healthcare payer and the standard-bearer that other insurers use as a model—bases its payouts on volume rather than on value.

Under this system, there is a positive economic incentive to deliver more care rather than better care since Medicare makes payments made irrespective of quality. Indeed, there is little or no incentive to make a proper diagnosis or choose the best treatment the first time around.

Among the many efficiencies that could be brought to this system, one shines brightest among proponents of personalized medicine: customize treatments based on individuals’ particular situations and especially on the basis of their genetic makeup. By one estimate, simply customizing the doses people get of the blood-thinning drug warfarin could save as much as $1 billion a year. The medicine is one of the most heavily prescribed in the country and can cause serious side effects if not calibrated precisely to a patient’s needs.

But there are a number of difficult hurdles to clear before we can realize that dream.

First, we must create a universally usable electronic health records system capable of managing, in a standardized way, the new kinds of genetic information that will be at the core of personalized medicine.

“At a time when information technology has transformed most other sectors, with particular benefit to the consumer, the health care sector, with its paper files, often inaccessible records, and incomplete patient data, stands out as primitive indeed,” Leavitt laments in the HHS report.

There is, at least, progress on this count. The department proposed standards for embedding genetic data and other family history information into electronic health records in 2008 and is in line to finalize those guidelines in 2009. HHS also set a national goal of getting most Americans switched over to electronic health records within five years, an ambitious if probably unrealistic aim.

But we will need a lot more than electronic records. By one account in the HHS report, patients (who are known in the lingo of personalized medicine as “consumers,” a worrisome shift in nomenclature I will address in a moment) will have to take on more of the job of keeping those records accurate and up to date with the help of “new consumer-friendly tools.”

For the most part we still don’t know when, if ever, medical professionals will understand enough of this information in a way that can really have a positive impact on people’s health or the national health care budget.

Take, for example, the time you generally spend at the beginning of a doctor visit, describing how you’re doing and giving the clues that a trained physician might recognize as medically important. That conversation “unnecessarily consumes precious time from providers,” according to a chapter in the HHS report contributed by Geisinger Health Systems. The solution? Spell out your woes to a touch-screen computer before the doctor comes into the exam room.

As it turns out, this is just one of several ways in which personalized medicine will demand a new (and rather impersonal) level of personal responsibility when it comes to health care. In fact, the hidden bomb in the word “personalized” in this new medical context is that it is going to be very much up to the “person”—that “consumer” we were talking about a moment ago—to decide how to deal with all the incoming information, including how to understand what it means and how to balance it against the economic realities of limited health coverage.

As the group FasterCures notes in the HHS report, a major hurdle for personalized medicine “is a lack of ‘genetic literacy’ among members of the general public. Informed patients are critical to patient-centered care, but as personalized medicine techniques become more sophisticated and information more complex, caregivers will face steeper challenges in communicating effectively with patients of all education levels and backgrounds.”

This education process will get even more dicey as doctors and other caregivers try to convince patents—er, consumers—to upload their personal medical information to giant databases in order to help researchers figure out what all these genetic signals really mean. “Discovery will come more rapidly if large amounts of clinical information are made available to researchers,” the report says. “The largest source of such information is ourselves,” it goes on, noting that this is one of the great advantages of getting people’s information into uniform “interoperable electronic health records”: It’s easier to suck personal data up into a data-crunching combine to speed discovery.

I did find one clause buried in those 299 pages acknowledging that “many issues, including privacy protection,” still need to be addressed.

No kidding.

Patient-consumers (or perhaps impatient consumers, waiting for that automated touch-screen to ask them where it hurts) are not the only ones who may find it difficult to adjust to the brave new world of personalized medicine. There are questions about whether pharmaceutical companies will find any economic incentive to develop medicines that are useful for only small, genetically specialized portions of the population. And then there is the looming question of how many of the countless genetic tests now under development are really going to prove themselves to be valuable at all.

As noted at a Personalized Healthcare Summit held in October, “Genetic and genomic knowledge relating to clinical outcome is missing – does value exist when these markers are used in a real clinical setting? The data don’t exist yet to guide physician action.”

In other words, for the most part we still don’t know when, if ever, medical professionals will understand enough of this information in a way that can really have a positive impact on people’s health or the national healthcare budget.

It doesn’t help that the Food and Drug Administration has opted not to regulate most gene tests, citing a shortage of resources; that HHS has so far resisted calls to create a proficiency testing program that would help ensure that test results are accurate and meaningful; or that the Medicare program for the most part does not reimburse for tests considered “predictive,” which pretty much blows the incentive to create these kinds of tests in the first place.

Health officials can say all they want to convince us “consumers” that it is empowering to take the reins of our own healthcare, but the truth is most people feel totally overwhelmed as it is and will be feeling even more so as health technology advances further. No wonder the HHS report acknowledges that the public may not be ready for personalized medicine.

“Patient education will play a prominent role in the acceptance of personalized healthcare, given that patients will need to become more involved in managing their own health portfolios….”

There’s a lot of work to be done by those designing this revolution before I’ll be waving a red flag at the barricades.

Rick Weiss is a Senior Fellow at the Center for American Progress and Science Progress.

Current estimates are that the number of Americans older than 85 will quadruple by 2050, to 18 million from today’s four million. A huge proportion of these people will require some kind of ongoing help with the tasks of daily living. Yet as spelled out last year in a Center for American Progress report by Lisa Eckenwiler, “Caring About Long-Term Care,” the vast majority of our elderly will not get the benefit of professional long-term caregivers because of the lack of resources or lack of available programs in their communities.

The worst thing that could happen is for people to gain extra years of life and wish, for lack of decent care, that they’d had an earlier exit.

In fact, 80 percent of the nation’s long-term care is provided by unpaid caregivers, mostly family and friends. There are many obvious benefits of keeping at least a portion of long-term care in the family, but it is not practical in many cases to expect family members to be able to carry the entire burden. At least 60 percent of those unpaid caregivers are already busy with their own jobs.

Meanwhile, few employers offer assurances of help for employees who need to care for aging relatives. And the Family and Medical Leave Act, which assures up to 12 weeks of unpaid leave for such purposes, still applies to only a fraction of employers and, if anything, has lately come under threat of being weakened by business lobbyists.

As yesterday’s report showed, the need is only going to grow. In 2006, the latest year for which data are available, U.S. life expectancy grew to a record high of 78.1 years, up from 77.8 a year earlier. Death rates from all the major killers dropped, including cancer, heart disease, stroke, high blood pressure and diabetes. In fact, diabetes dropped from the No. 6 leading killer to No. 7, overtaken by Alzheimer’s disease.

In large part this reflects a payoff of years of basic research by federally funded researchers, especially those supported by the National Institutes of Health, according to Robert Palazzo, president of the Federation of American Societies for Experimental Biology. “Thanks to NIH research, millions of deaths from heart disease have been averted, millions more people have survived cancer, and deaths from diabetes have decreased dramatically,” he said in a statement. Yet as Palazzo and others have noted with increasing alarm, the $27 billion agency—considered the crown jewel of U.S. biomedical research—has been flat-funded for five years now.

Clearly we need to renew our nation’s commitment to high-quality research aimed at understanding the mechanisms of the major diseases. But at the same time, we need to develop a comprehensive approach to caring for all the people who will benefit from those discoveries. Eckenwiler notes that among the problems contributing to the long-term care crisis is an overemphasis on research relating to acute medical problems, and an inadequate research focus on medical and social management of the chronic conditions that lower the quality of life for long-term survivors.

This fragmented approach to medicine, which emphasizes specialists focused on their part of a patient’s problems instead of taking a holistic approach to patients’ needs, is out of step with the rising longevity of the American people. And this fragmentation is mirrored in the conflicting payment structures for different kinds of care.

In the short term, it will be important to protect and even strengthen or broaden the protections of the Family and Medical Leave Act. The worst thing that could happen is for people to gain extra years of life and wish, for lack of decent care, that they’d had an earlier exit.

Rick Weiss is a Senior Fellow at the Center for American Progress.

An alarming number of countries are failing to provide the most basic health services that would save lives, with 30 percent of children in developing countries not getting basic health intervention such as prenatal care, skilled assistance during birth, immunizations and treatment for diarrhea and pneumonia.

Wide disparities in health care for the poorest and best-off children are seen even in the highest-ranked countries, the report said.

…

Use of existing, low-cost tools and knowledge could save more than 6 million of the 9.7 million children who die yearly from easily preventable or curable causes, the report [by Save the Children] said.

They include antibiotics that cost less than $0.30 to treat pneumonia, the top killer of children under 5, and oral rehydration therapy—a simple solution of salt, sugar and potassium—for diarrhea, the second top killer.

This is as much a failure on the part of the rich developed world as it is one on the part of governments in the developing world. In addition to financial aid, there needs to be a focused effort to help developing countries set up sustainable primary care networks in socially and economically disadvantaged areas.

But a British study published in 1998 drew a link between the measles-mumps-rubella vaccine and autism. While the study itself was flawed and discredited, and subsequent research has demonstrated no link between vaccines and autism, parents and advocacy groups are still wary.

To learn more about vaccine safety, Science Progress spoke with Dr. Saad Omer, the associate director of the Institute for Vaccine Safety at the Johns Hopkins Bloomberg School of Public Health. Parents concerned about vaccine safety, he says, are coming from the right place in terms of their desire to protect their children, and that it is the responsibility of the public health community to broadcast the right information so that people can make informed decisions about the risks and benefits of vaccines and vaccine-preventable diseases. This interview has been edited.

Andrew Plemmons Pratt, Science Progress: Some recent media coverage has focused on the March ruling from the National Vaccine Injury Compensation Program to Terry and John Poling, who claim that a vaccine contributed to their daughter Hannah’s development of autism. In a New York Times editorial, Paul Offit of the Children’s Hospital of Philadelphia laments the fact that the program abandoned a previous standard for a “preponderance of evidence” for determining the link between vaccines and injuries and instead ruled that their claim was made on standards of “biological plausibility.” Is there a problem with the way that vaccine injury compensation program ruled on this issue, and what does it say about the way we are approaching vaccines in general?

Dr. Saad B. Omer: Let me start with the case, to briefly describe it for those who are not familiar with it. It was a case of a nineteen-month-old girl who received several vaccines together after a delay due to current bouts of otitis media, or an ear infection. And so those vaccines were administered together and she developed some symptoms after that, and at the twenty-three month assessment she was diagnosed with having mild symptoms of autism spectrum disorder, and during her evaluation she was diagnosed with a mitochondrial disorder. A claim was filed in a federal court, and the government settled, awarding them compensation for that.

So to put things in perspective for that case—and in terms of people drawing conclusions from it—I would caution that this is just a case and the question I often ask, even within the scientific community is “where are the controls?” Because when we assess scientific evidence, we need to keep in mind that we need to compare an association of an event with an outcome in both cases and controls, we haven’t had that kind of evaluation yet. And I can go into specific examples of what problems one can have. However, this is a “biologically plausible hypothesis.” What does that mean? That means we should explore this kind of hypothesis under a counterfactual model but should not draw conclusions from it at this point.

And just to clarify why we are on this topic: even if this link is established, and what it says is that mitochondrial disorders, which are a kind of disorder in the cell’s energy mechanism, is proven to be exacerbated by vaccines and result in autism spectrum disorders, metabolic disorders are very rare and it would explain a very small proportion of autism diseases—just to put that in perspective.

Now to the second part of your question, about the change in the standard in the vaccine court that resulted in the awarding of this compensation. First of all, it wasn’t the injury compensation program that changed it, it was the interpretation of a couple of circuit court decisions. These higher court decisions were the result of some cases from the compensation program that were appealed and there were a couple of decisions which the Special Masters of the compensation program, not the HHS, interpreted as having said that the evidence should be evaluated on a standard of “biologically plausible.” I think that’s dangerous, because I can sit here and come up with twenty or thirty different hypotheses which would be biologically plausible on several biological models. We are not talking about probable; we are talking about plausible. Even with probable models, we know the human body is complex, and if you test twenty different biological hypotheses, a majority of them won’t pan out in humans. So I think it’s not a very robust standard to go by because what we are saying is that we would have judgments on these cases based on something that could happen, not something that does happen.

SP: The government has programs that do vaccine surveillance and maintain safety. Could you talk a little bit about what those programs are and how effective they are?

Omer: One major program is the Vaccine Adverse Events Reporting system, which is jointly managed by the CDC and the FDA, and events that seem to be associated with vaccines are reported into that system. It’s a good system for generating signals but it has its limitations. The major limitation is that we don’t have a good denominator to calculate rates so we cannot assume all the vaccine doses that entered the market were administered, so we don’t know the rates.

But another interesting problem that has come up is due to the fact in the U.S. adverse event reporting system, anyone can report a case into the system. There was a recent analysis published in Pediatrics that showed that most of the rise in reports of autism-related symptoms associated with vaccines has been due to increased reporting of litigation-associated cases. So we have that kind of a problem with VAERS but it still has a lot of utility in terms of generating signals. For example, it generated a signal for the old rotavirus vaccine.

Then the CDC has the Vaccine Safety Datalink. They have put together a system by linking databases from several large HMOs, and it covers approximately two percent of the U.S. population of zero to six years. Fortunately because vaccine events are rare, you need large databases to get enough numbers and do a robust scientific study, so that’s a good system.

Then there is the Clinical Immunization Safety Assessment Network, which is a network of a few centers of excellence, mostly academic centers, coordinated by the CDC, to assess vaccine safety in a clinical setting.

So this is basically what the vaccine safety system is in the U.S. However I must say, I think vaccine safety needs a lot more resources than it is provided. Because as I said, vaccine events are rare so you need large numbers to study these phenomena and the resources that are available are very low.

SP: These are very personal choices that parents are making about whether or not to exempt their children from getting vaccinations. What do you say to parents who might be thinking of exempting their children from getting vaccines because of what they might have heard about these possible links to autism?

Omer: There have been several studies—both in the U.S. and outside, in Denmark and other parts of Europe—that have looked at the issue of vaccines and autism and we haven’t found any credible association between vaccines—either thimerosol, which is a mercury preservative that was of concern a few years ago—and MMR, the measles mumps and rubella vaccine and autism. So there have been several studies, and our website, vaccinesafety.edu, discusses some of these issues so people can go and look up specific evidence related to that.

On the other hand, we know that there is risk of—even an individual level risk—of acquiring vaccine-preventable diseases in the United States if your child is not vaccinated. For example, in a national-level study it was found that kids who are exempt from vaccination requirements had thirty-three times—not percent, it’s times—higher risk of acquiring measles with those who are vaccinated, who do not seek exemptions, and [in a Colorado study] six times higher risk of acquiring pertussis than those who are vaccinated. So there are real risks involved in terms of acquiring vaccine-preventable diseases

One last point in this regard: we do know that congenital rubella syndrome is associated—and there are some studies showing an association—with autism-like symptoms. So we know that part of that syndrome is explained by a congenital rubella syndrome which used to occur when the population-level immunity in the U.S was relatively low. So actually, MMR vaccine prevents against something that is associated with autism. So if you are thinking specifically in terms of autism, one should consider that we are talking about something that prevents autism. Congenital rubella syndrome is when mothers get rubella in pregnancies, and children develop certain abnormalities.

SP: So in your experience, where does this misinformation about the risks of vaccination come from? Is it usually generated through parents talking to parents? Is it the media? Is it doctors talking to parents?

Omer: It’s several sources. We found in our studies—looking at parents of children exempted from vaccination requirements, compared to those vaccinated—there was an association with types of provider, trust in government, the sources of information people tended to get, information from some of the advocacy sites tended to seek exemptions at a higher rate, etc. So yes. There are several sources of that, and there are passionate people who feel there is an association with vaccines and autism, and that includes some celebrities as well. So that gets people’s attention.

On the other hand I must say that most parents, even those that are concerned about vaccine safety, are coming from the right place. All of us want our children to be safe from any harm, including harm from any pharmaceutical interventions. So we shouldn’t be dismissive of that, but it’s our responsibility, for those of us in the public health community, to put out the right information so that people make a truly informed decision about the risks and benefits of vaccines and vaccine-preventable diseases.

SP: What do you think is most important for people who are both working in the public health community, people who are policymakers, people who might be hearing about this issue, and for parents to take away from this whole conversation in the public sphere at the moment?

Omer: One thing that people should realize is that we know that vaccines have some side effects. And we should acknowledge that, everyone who is involved. However, the risk and benefit calculus for all vaccines that are out there, based on our current knowledge, heavily favors not only getting your child vaccinated, but also getting them vaccinated according to the specified schedule. I have seen a new trend where people are splitting the difference and saying, “OK, I’m going to get my kid vaccinated, but I’m going to get them vaccinated late.” Well the risk of illness is not constant across childhood and so that’s why the Advisory Committee on Immunization Practices and the American Academy of Pediatrics come up with these recommendations to look at several factors, including the burden of disease. So it’s important to not only get your child vaccinated, but also to get them vaccinated per specified schedule.

It is an apt moment to consider these issues: this Friday, April 25 is National DNA Day. But genetic medicine is ultimately about helping real people live healthier lives, and discussions about genetics and public policy must not lose sight of the men, women, children, and parents who seek professional help in unraveling their own genetic code.

To help patients understand the complexity of information about their own DNA, or the DNA of their family members, genetic counselors fill a pivotal role in the healthcare system. To learn more about how medicine can guide individuals to an understanding of their own genomes, Science Progress spoke with Barbara Bernhardt, a genetic counselor, clinical associate professor of medicine at the University of Pennsylvania Medical School, and Co-Director of the Penn Center for the Integration of Genetic Healthcare Technologies. This interview has been edited.

Andrew Plemmons Pratt, Science Progress: For those of us who might not be familiar with the field in general, can you tell us what genetic counseling is and what its goals are?

Barbara Bernhardt: Genetic counseling involves providing individuals with information about genetics that might pertain to their health. We have two goals: educating people about the role of genes and disease and also helping them use that information to make decisions that relate to their own health or reproduction.

SP: Based on the current genetic testing technologies that we have, what are the usual situations in which patients might seek genetic counseling in order to use their personal information to make healthcare decisions?

Bernhardt: At this point in time, the usual reasons for having genetic counseling or testing are different depending on whether we’re talking about reproductive issues, pediatric issues, or adult issues. In reproduction, people use genetic testing, first to see if they are at an increased risk of having a child with a particular kind of genetic disorder. Couples get screened to find out, for example, if they are carriers for cystic fibrosis. There is also genetic testing that can be done on the developing fetus to find out if the fetus has a genetic disorder.

In pediatrics we use genetic testing when we suspect that there might be a problem in a child, either a newborn or a younger child. Often we consider testing for children born with birth defects, who may have developmental delays or may have certain specific conditions that we believe are genetic, and a diagnostic genetic test can determine if that is in fact what they have.

In the adult settings where I work now, we see people who may have a genetic disorder, and again we may use a genetic test to diagnose a genetic condition. Or we may be doing genetic testing to find out if somebody is susceptible to developing a genetic disease. These susceptibility tests are the kind of tests that are just taking off now and their use will continue to grow in the future.

SP: What sort of susceptibilities might people be tested for?

Bernhardt: At this point in time, most genetic testing for susceptibility is taking place in cancer, particularly with regard to susceptibility to breast and ovarian cancer, and also to colon cancer and related cancers. There is going to be an increasing amount of testing to find out about susceptibility to other common disorders of adulthood—things like cardiovascular disease, or neurological disorders like Alzheimer’s, and Parkinson’s disease. There is going to be a growing list.

SP: Various companies are beginning to offer direct-to-consumer genetic testing for individuals and the price of these tests is falling very quickly. Is this a good thing? As a genetic counselor, are you worried that patients might have their DNA sequence misinterpreted, leading them to making problematic health care decisions?

Bernhardt: Well I don’t think we really have enough experience to know what’s going to happen. Nor do we have a whole lot of information on how commonly people are getting tested. The kind of testing that is being done now is to test people for small changes in their DNA that might indicate a slightly increased risk for some common disorders and some traits. So the way people are getting risk information is in terms of relative risk. They are being told, for example, that you have a one and a half times higher risk for developing heart disease or developing hypertension, for developing Parkinson’s, for developing restless leg syndrome, than the average person in the population. I’m not sure how meaningful those kinds of risks are to people.

It remains to be seen how people are going to interpret those risks and, more importantly, what they are going to do about them. I think it would be great if we all knew that we were at risk for heart disease so we exercised more, reduced fat in our diet, didn’t smoke, and took much better care of ourselves. But I don’t know if people are going to act on the kind of results that they get.

SP: Are these tests going to be providing people with information that you think is particularly conclusive, or are we talking about indicators of small rises or decreases in susceptibility?

Bernhardt: For the most part, they are not diagnostic tests. There are a few tests out there from at least one company where they are testing for changes in specific genes that we know cause disease, and those are actually diagnostic tests, rather than susceptibility tests.

SP: Well that seems like an important distinction. Genetic discrimination has gotten a reasonable amount of exposure in the mainstream media recently, especially in the stories on genetic testing and its ethical implications that won Amy Harmon a Pulitzer Prize this week. How real is this threat that she and others have written about—discrimination by insurance companies or employers? Is there a risk that people will refrain from sharing the results of genetic testing with their health care providers?

Bernhardt: The fact of the matter is that fear of genetic discrimination is high in the public. But actual examples of genetic discrimination are quite few. So we have a disconnect between reality and concern. The theoretical concern is great, and in terms of genetic discrimination, it really depends on what kind of marketplace or area you’re thinking of. I think there’s a real possibility of genetic discrimination by companies that sell long-term care insurance or disability insurance. I think there’s less of a concern in the health insurance marketplace, primarily because most people get insurance through large employers—where there is no individual under-writing—and because many states have laws in place that prohibit discrimination in the health insurance market.

However, when you survey the public, most of their concerns are with regard to health insurance. If they get a genetic test that shows they are susceptible to something like breast cancer, they fear that they would lose their insurance, they will be charged more for insurance, or that something bad will happen. Examples of that are very, very few and far between. Nonetheless, the fear is high, and because of this, some people will avoid genetic testing, and some may not share information with their health care providers.

SP: What about questions of access? Not everyone in the United States has health coverage, and not everyone in the United States can necessarily afford this kind of genetic testing. Is that going to create inequalities beyond the existing lack of coverage?

Bernhardt: I think it certainly will, and even when we’re talking about the kinds of genetics tests that we order in our genetics clinic, which are diagnostic tests to diagnose genetic disorders, we sometimes are not able to get those tests covered for people who do have health insurance. So access issues already exist. These tests tend to be quite expensive. So it has already been a problem getting existing technologies made available to all citizens.

SP: Some of your past research is focused on the economic impact of genetic technologies for health care providers. Is this advent of personalized medicine and individual genetic testing going to have an impact on health care costs?

Bernhardt: That’s an unanswered question. Certainly, that is a concern: If people find out they are susceptible to something, they are going to request additional testing. On the other hand, there’s the hope that if people find out they’re susceptible to something, they may change their behaviors, so that they reduce their risk of ever developing an expensive disease. It’s an open question that we really need some time to work with.

SP: What else should people understand about the public policy implications of genetic testing?

Bernhardt: This is an area that is still fraught with a lot of uncertainties. Public perception is that as we begin to discover more genes that are associated with different disorders, we will have increased certainty about being able to predict someone’s susceptibility to developing a disease, and also to make a recommendation for reducing that risk. I think the public needs to be aware that we’re not always able to do that. So we all need to tread cautiously as we approach issues relating to new genetic technologies. My hope is that as we learn more, we’ll be able to make better recommendations: we’ll be able to improve the health of the population, and we’ll be able to have some cost savings. But the reality is that we are a long, long way from being able to do that.

The incident simply points to a larger problem: Federal policy regarding comprehensive reproductive health care is inadequate.

Last week, researchers at the University of California, San Francisco, uncovered this ironic situation while trying to “connect” to “reproductive health literature.” Health care providers, researchers, and advocates around the country were alarmed to learn that POPLINE (POPulation information onLINE), had rendered the search term “abortion” a stopword—which directs the database to ignore the term when used in a search. UCSF librarians discovered this deliberate restriction when they were unable to find a single document containing the word “abortion” in POPLINE’s database, and contacted the administrators at the Johns Hopkins Bloomberg School of Public Health to ask them why. Simply put, the UCSF librarians were told that “abortion” was eliminated as a search term by the POPLINE administrators so that the latter could examine the database for information “that might not have been consistent” with guidelines from a government agency that funds the project. And our UCSF colleagues were then given some mystifying, convoluted search term suggestions for finding medical literature on the subject, including “fertility control, post-conception” and “pregnancy, unwanted.”

By Friday morning, news of the self-censorship had spread like a virus. Countless members of the medical, scientific, and advocacy communities responded and by early Friday evening, Hopkins Dean Michael J. Klag issued a statement unequivocally denouncing the administrators’ decision to censor the word abortion and promising to get to the bottom of it. By Tuesday, he issued a follow up statement citing his opposition to the decision and his speedy response, while blaming “an overreaction on the part of POPLINE staff” to a search by USAID [United States Agency for International Development] officials who “found two items in the POPLINE database that advocated for abortion.”

So let’s pause for a moment and review what happened: a vigilant literature search on the word “abortion” by unidentified Federal employees at USAID resulted in finding two abortion articles in the POPLINE database that they deemed to feature inappropriate advocacy. Once notified by the Feds, Hopkins administrators immediately made abortion a stopword—an additional step not requested by USAID, but implemented to allow administrators to search for other material that might have been inconsistent with the agency’s guidelines—effectively ending access to abortion research to health professionals and the public on their 30-year-old database.

While giving credit to Dean Klag for his quick response to an untenable situation, there are two important questions that remain: Why are Federal employees at USAID so attentively monitoring scientific research articles on the POPLINE database for the word “abortion”? And why are Hopkins administrators so afraid of them? The Dean states that USAID is prohibited by law from funding any abortion activities or supplies. This is all the more reason for concern by researchers, civil libertarians, health care providers, and patients who deserve the best possible care. But the incident simply points to a larger problem: Federal policy regarding comprehensive reproductive health care is inadequate.

The Real Impact of Limiting Access to Information

The medical and scientific needs of the reproductive health professional community were impeded by POPLINE’s decision to remove abortion as a search term on its publicly funded database. If this action had gone unchecked, the decision would have limited the medical and scientific community’s ability to access information on a range of patient care scenarios, including women experiencing both wanted and unintended pregnancies.

A clinician seeking information while providing abortion care services would have been unsuccessful in accessing key medical and scientific literature on the topic—potentially endangering the patient. Women with wanted pregnancies and their health care providers looking for information on spontaneous abortion (miscarriage), inevitable abortion, incomplete abortions, missed abortions, and related medical information would have also been denied this key data.

Unsafe abortion practices claim thousands of lives worldwide every year and any public health student, policy maker, or provider seeking vital information on the topic of unsafe abortion would have also come up empty-handed.

Ideology Trumping Science Is About More Than Just Abortion

The specter of ideology trumping science goes way beyond POPLINE and abortion. There is more visible political opposition to important health classifications like family planning, sexuality, and reproductive health than we have seen in years. Political posturing can get in the way of science, public health, and patient care—even POPLINE’s reputation is potentially at risk.

Even self-censorship of a specific term like “abortion” in a scientific setting—especially as a result of Federal government monitoring—sets a dangerous precedent.

Over the last seven years, we have witnessed an intentional blurring of the lines between opposition to abortion and a more general objection to contraception. For example, many of President Bush’s anti-choice family planning political appointees have been openly anti-contraception as well. Bush’s 2002 appointment to a key FDA panel, Dr. Joseph B. Stanford, complained about contraceptive use even among married couples. And more recently Bush appointed Susan Orr as the acting deputy assistant secretary for population affairs to oversee family planning funding for clinics serving poor women, even though she previously worked to limit access to contraception as the senior director for marriage and family care at the Family Research Council, an organization well-known for its anti-contraception stance.

And now the term “reproductive health” is being targeted. At the United Nations, there are unbelievably rancorous debates about whether or not to include the terms “sexuality” and “reproductive health” in treaties because many politicians view them as faux terms for abortion.

It may have been that POPLINE staff made the decision based on fear of losing their USAID funding. USAID does have a history of basing reproductive care funding decisions at least partly on ideology and politics. For example, they have withheld funding from developing countries if potential grantees provide abortion services or give abortion referrals to women.

It’s also possible the suggestion came from above. With the Bush administration’s history of attempting to (and often succeeding in) restricting access to abortion services and information at every possible turn, it’s not so unlikely they’d attempt to scrap the word altogether.

The bottom line is that even self-censorship of a specific term like “abortion” in a scientific setting—especially as a result of Federal government monitoring—sets a dangerous precedent. We must follow the example of our UCSF colleagues and make preserving access to reproductive health science a part of our own work plans. It’s scary enough to consider the possibility that ideological searches are being performed by anonymous government employees who troll our scientific databases for the word “abortion.” “Contraception,” “sexuality,” and “reproductive health” are the next stopwords, unless we remain vigilant and protest loudly.

Pablo Rodriguez, MD, is the Board Chair of the Association of Reproductive Health Professionals. Wayne C. Shields is the President and CEO of the Association of Reproductive Health Professionals. Jennifer Aulwes is the Media and Policy Manager for the Association of Reproductive Health Professionals.

Hill Heat glosses the past few tumultuous weeks for EPA administrator Stephen L. Johnson, who was hit with a tidal wave of criticism for denying California’s Clean Air Act waiver request and is now failing to cooperate with congressional investigations into the matter.

Ed Silverman at Pharmalot asks if publicly financed clinical trials would better protect the public and lower the cost of new drug testing.

Defense Tech reports that U.S. military officials are concerned about the national security threat of adversaries tapping into online mapping services like Google Maps to obtain vital intelligence.

Liz Borkowski at The Pump Handle offers a nuanced assessment of this week’s news about testing that revealed trace amounts of pharmaceuticals in drinking-water supplies and the rationales for disclosing and not disclosing the information.

Respectful Insolence responds to the recent “Broken Pipeline” report on NIH funding problems by arguing that universities share a part of the blame for the troubles of young scientists.

Craig Venter announced at the TED conference that he plans to develop fuels using living cells that consume carbon dioxide and generate fuels like methane gas. “The only way we think biology can have major impact–without increasing the cost of food or limiting its availability–is to start with carbon dioxide as a feedstock,” he said during his presentation. He referred to this project as the “fourth generation” of fuels, and he said he hopes to develop the technology within eighteen months.

A Federal Advisory Committee on Immunization Practices recommended unanimously on Wednesday that all children over the age of six months should be vaccinated for influenza every year. The Centers for Disease Control and Prevention are expected to adopt the recommendation within the next two years. “I’m very excited about this,” said Dr. Carol Baker, a member of the committee and president of the National Foundation for Infectious Diseases. “As a pediatrician, it is my responsibility to protect my patients from influenza,” she said. Critics of the recommendation emphasized possible risks of heavy metal poisoning from vaccinations. “The CDC continues to minimize the dangers of injecting mercury and aluminum into our kids,” said Rita Shreffler, executive director of the National Autism Association. The CDC claims that those risks have not been confirmed scientifically.

Who should be the next President’s science adviser? Scientists could help decide the fate of the position and the 50 or so science-and technology-related vacancies opening up when the new administration takes power in January. Speaking at the annual American Association for the Advancement of Science meeting, policy experts told scientists to organize and weigh in with a list of recommendations for the positions. They should also lobby for the restoration of a science advisor who reports directly to the President, a position removed during the Bush administration, reported Science.

Google has teamed up with the Cleveland Clinic to store patient’s medical records online. The pilot program has raised alarms among privacy watchdogs who are concerned the search engine giant will exploit the information for marketing purposes. The program, which has yet to specify a start date, will begin with 1,500 to 10,000 volunteer patients.

The United States Supreme Court ruled 8 to 1 on Wednesday that medical device makers are immune from liability for injuries as long as the devices were previously approved by the Food and Drug Administration. The legal question behind the case pertained to whether or not Federal law (specifically, the Medical Device Amendments to the Food, Drug, and Cosmetic Act) can preempt state-based lawsuits. Next Monday, the Supreme Court will hear another FDA-related case which explores further the rights of states to challenge FDA decisions.

The Centers for Disease Control and Prevention have been fairly successful over the years in predicting the most virulent flu strains and then formulating vaccines based on those predictions. This year was an exception. The current vaccine is most effective against fewer than half of the strains that are most dominant in the human population. Government researchers are presently deciding which strains next year’s vaccine should target, and they have decided, in an unusual move, to leave out two of the strains targeted by the present vaccine and replace them with two new strains next year. How well vaccine makers will adapt to the CDC decision in time to produce 100 million doses by the fall remains to be seen. The Knight Science Journalism Tracker has a full roundup of coverage.

SciDev.Net reports that the first step is creation of a web-based database. The program will launch May 12. The database, which will house information on members and their research, aims to link researchers working in similar fields and prevent unnecessary overlap, and allow individuals and organizations to request specific resources.

Evelyn Strauss, executive director of the new organization, explained the mission of the new group to SciDev.Net:

The “Without Borders” idea perfectly captures what we — and others in different fields — are trying to do: break down the geographical (and other) borders that can hinder progress, and engender the sense of belonging to a global community.

The initiative will begin with a focus on African countries. Already, there are 70 organizations and 400 individuals around the globe willing to participate.

Pharmaceutical companies justify massive marketing budgets, which drive up drug costs, by citing large numbers of drug handouts. They claim that these free samples often go to the uninsured, who might not otherwise be able to afford these drugs. But according to the Chronicle, “More than four-fifths of the people receiving the freebies were covered by insurance all year…The groups that received a disproportionately high number of freebies were patients who were white… and had better access to medical care.” In addition to the disparity of access, there is also an increased likelihood that doctors will prescribe a drug that might not be right for the patient just because it is free.

The study demonstrates that pharmaceutical company marketing tactics that seem beneficent do not adequately compensate for a fundamentally flawed healthcare system that does not mandate a minimum level of care for all citizens regardless of income. Nevertheless, the Pharmaceutical Research and Manufacturers of America, a trade group, issued a statement saying that the studies, which use data from 2003, were “fatally flawed” since they do not take into account the outreach program that that the industry began in 2005. The statement goes on to point out that even though doctors are likely to consider patient income when giving free samples during an office visit, the uninsured often cannot make office visits in the first place.

But this is not the only recent news underscoring the threat an inequitable care system poses to public health. In an editorial published today, The New York Times argues for universal coverage and cites another study by Harvard Medical School finding that “uninsured near-elderly people got sicker at a faster rate than comparable people with insurance. Those disparities were sharply reduced when people turned 65 and became eligible for Medicare.” The NYT also pointed to a study from the American Cancer Society indicating that uninsured patients were less likely to receive cancer screenings, which means that cancers can go undetected until they progress and become more difficult to cure.

The inequities of the health industry present public health risks to an unacceptable number of Americans, and these recent studies provide more hard evidence of this unsustainable situation.

Image source: AP.